The reproductive function is carried out as a complex sequence

physiological processes occurring in the body of the father, mother, fetus. Toxicants can have

adverse impact at any stage of the implementation of the function. The complexity of the phenomenon of reproduction

makes it highly vulnerable to xenobiotics. The difficulty of understanding the phenomenon lies in the fact that

reproductive disorders may be the result of even an acute toxic effect on various organs

and systems of one of the "participants" of the process, in different time periods, and appear only later

many months, and sometimes years, defects in conception, gestation, fetal development and insolvency

growing organism (Table 1).

Table 1. Periods of the implementation of the reproductive function, vulnerable to the action of toxicants.

Preconception period

Puberty

sex drive

Formation of sex cells (gametes)

Gamete transport

concept period

Fertilization

Oocyte implantation

Development of the placenta

Pregnancy

embryo development

fruit ripening

Birth

postnatal period

Lactation

Growth and development of the child

Development of the sex organs

Formation of intelligence

Transplacental carcinogenesis

1. Brief description of the anatomical and physiological features reproductive organs

The female reproductive system consists of 4 anatomical structures, the function of which

regulated by hormones produced by the pituitary gland, ovaries, placenta.

The ovaries are an almond-shaped paired organ located on either side of the uterus.

The functions of the ovaries are ovogenesis, i.e. the formation of female germ cells (gametes - oocytes) and the production

steroid hormones (estrogen, progesterone). Oogonia are formed during fetal development

fruit of the future female body. In the body of a woman, only the maturation of eggs occurs. One

the egg (second-order oocyte) matures alternately in the left and right ovaries of a woman

at two months.

Fallopian tubes - channels that connect the ovary with the lumen of the uterus. This is the confluence of male and

female germ cells and the pathway by which an ovulated oocyte travels to the uterus.

The uterus is a hollow organ, with powerful muscular walls, located in the pelvic cavity. Anatomically

The uterus is divided into four sections: fundus, body, isthmus, and cervix. The wall of the uterus consists of three layers:

endometrium (mucosa lining the uterine cavity, into which it implants and where it matures

fertilized egg), myometrium (muscle tissue that ensures the release of the fetus during childbirth),

The vagina is a formation that connects the uterine cavity with the external environment.

The male reproductive system consists of four organs, the functions of which are regulated

hormones produced by the pituitary gland and testicles (testicles).

testicles - paired organ located in the scrotum, in which the male reproductive organs are formed

cells (spermatozoa) and steroid hormones are synthesized (Leydig cells synthesize

testosterone). Developing sperm goes through the stages of spermatogonia, spermatocyte of the first order,

second-order spermatocyte, spermatid and sperm. In humans, the process of sperm maturation takes

approximately 70 days.

The epididymis is a convoluted tubular structure that connects the testis with the efferent tubule (canal,

allowing sperm to enter the urethra). The function of the appendage is to provide conditions for

spermatozoa maturation and release.

The urethra is a channel in which two sections are distinguished: prostatic and passing through the penis.

The urethra connects the efferent tubule with the external environment.

2. Development of the fetus

Fertilization occurs in the fallopian tubes and consists in the fusion of the female germ cell and

spermatozoa. The fertilized egg is transferred to the uterus, where it is implanted in the endometrium (period

implantation). During this period, which lasts about 2 weeks, the cell, due to its great autonomy from

organism of __________ mother, little sensitive to the action of toxicants. If in this period the mother's body

damaged to a large extent, the egg dies, spontaneously aborted and the pregnancy is not

is diagnosed. After implantation of the cell, the embryonic period of development begins,

lasting up to 6 - 7 weeks after conception. During this period, sensitivity to toxicants is especially

great. In the case of their action on the mother's body, the formation of large morphological

fetal developmental defects or death. The embryonic period is followed by the fetal growth period.

(fetal period). In this period, the sensitivity of the developing organism to toxicants

constantly changing. Each organ of the fetus, forming in different times, has its own critical

the period of highest sensitivity to xenobiotics. Usually organogenesis is completed in the first

trimester of pregnancy, but the development of the genitals and the central nervous system continues after

the birth of a child.

3. Features of the effect of toxicants on reproductive functions

To accurately identify the mechanism underlying reproductive disorders, sometimes practically

impossible, since the xenobiotic could affect either both parents, or only one of them.

them, or on the mother and fetus.

Adverse effects of toxicants (and their metabolites) on male and female organs

reproductive system may be due to either a violation of the mechanisms of physiological

regulation of their functions, or direct cytotoxic effects. Yes, hormonal imbalance

regulation of ovarian function may be due to the competition of xenobiotics with sex hormones

(androgens, contraceptives), actions on estrogen receptors (organochlorine and

organophosphorus compounds), changes in the rate of production of sex hormones, their metabolism and

excretion (DDT, TCDD, PCB, chlordane). For example, polyhalogenated biphenyls disrupt

sex hormone metabolism. When administered to newborn rats, these substances significantly

change the function of the liver, significantly changing the level of sex hormones circulating in the blood. V

Subsequently, this leads to a violation of the fertility of animals.

Cytotoxicity, as a rule, underlies the damage to the germ cells of the father or mother and cells

embryo.

The mechanism of action of many toxicants remains unknown (carbon disulfide, hydrocarbons).

Some of the hazardous substances that may interfere with reproductive functions are presented in Table 2.

Table 2. Substances suspected to impair reproduction

1. Steroids

Androgens, estrogens, progestins

2. Anticancer drugs

Alkylating agents, antimetabolites, antibiotics

3. Psychoactive drugs, substances acting on the central nervous system

Volatile anesthetics (halothane, enflurane, methoxyflurane, chloroform)

4. Metals and trace elements

Aluminium*, arsenic, boron*, beryllium, cadmium, lead (organic and inorganic compounds),

lithium, mercury (organic and inorganic compounds), molybdenum, nickel, silver*, selenium, thallium

5. Insecticides

Hexachlorobenzene, carbamates (carbaryl), chlorobenzene derivatives (methoxychlor, DDT), aldrin,

dieldrin, FOS (parathion), others (chlordecone, ethylene oxide, mirex)

6. Herbicides

2,4-D; 2,4,5-T

Rodenticides

Fluoroacetate*

7. Nutritional supplements

Aflatoxins*, cyclohexylamine, dimethylnitrosamine, glutamate, nitrofuran derivatives, nitrite

8. Industrial toxicants

Formaldehyde, chlorinated hydrocarbons (trichlorethylene, tetrachlorethylene, TCDD*,

polychlorinated benzofurans*), ethylene dibromide, ethylene dichloride, ethylene oxide, ethylenethiourea,

ethylene chlorohydrin, aniline, plastic monomers (caprolactam, styrene, vinyl chloride, chloroprene), ethers

phthalic acid, polycyclic aromatic hydrocarbons (benzo(a)pyrene), solvents

(benzene, carbon disulfide, ethanol, glycol ethers, hexane, toluene, xylene), carbon monoxide, methyl chloride,

nitrogen dioxide, cyanoketones, hydrazine, aniline

9. Other products

Ethanol, components tobacco smoke, fire extinguishing agents (tris-(2,3-dibromopropyl) phosphate),

radiation*, hypoxia*

* - factor affecting mainly men

Substances that cause predominant damage to the male reproductive organs,

are presented in table 3.

Table 3. Substances that cause predominant damage to the male reproductive organs

Target Toxicant

spermatogonia

spermatocytes

spermatids

Sertoli cells

Bisulfan, procarbazine

2-methoxyethanol, procarbazine

methyl chloride

dinitrobenzene, hexanedione

Leydig cells

Epididymocytes

accessory sex glands

Ethane dimethylsulfonate

Chlohydrin, methyl chloride, ethane dimethylsulfonate

Imidazole

Reproductive characteristics in the postnatal period can be influenced by xenobiotics,

entering the body of a nursing mother and excreted with breast milk. Substances such as

metals (mercury, lead), tetrachloroethane, halogenated aromatic hydrocarbons (dibenzofurans,

biphenyls, dioxins), pesticides (DDT, dieldrin, heptachlor, etc.) can enter the body

newborn this way in large quantities.

Most often, in violation of reproductive function, they encounter polygenic (effect on

various organs and systems), multifactorial (the action of several toxicants), synergistic

(unidirectional spontaneous and toxicant-induced developmental disorder) action.

The main manifestations of toxic action chemical substances on organs and tissues

responsible for the reproductive functions of the body, and directly on the fetus, are: infertility and

teratogenesis.

3.1. Teratogenesis

The literal translation of the term "teratogenesis" means "the birth of monsters", from the Greek teras,

meaning "monster". In ancient times, it was believed that the birth of a deformed child with

anomalies of development is a consequence of the incest of man and deity. In the Middle Ages,

the fact that happened was considered as the result of the machinations of the devil, and, as a rule, the child and mother

sentenced to death.

Modern teratology as a science began to take shape in the forties of the twentieth century after

works by Warknay and collaborators who showed that the influence of factors environment such as diet

mother or the effect of radiation, significantly affect the intrauterine development of the fetus

mammals and humans. Earlier studies performed on fish, amphibians, chicken

embryos showed a high susceptibility of living beings to the action of adverse factors

environment, however, left doubts that mammals are subject to similar influences.

It was believed that the placenta reliably protects the fetus from harmful effects. In the 1950s - 60s the concept

the insurmountability of the placental barrier was shaken by the birth of thousands of children with congenital

developmental defects, women who took during pregnancy, as it seemed, practically

harmless sedative drug thalidomide. The problem of chemical teratogenesis has become a reality.

Teratogenic is the effect of a chemical on the body of the mother, father or fetus,

accompanied by a significant increase in the probability of the appearance of structural

functional disorders in offspring. Substances with teratogenic activity

called teratogens. There is an idea according to which almost any chemical

a substance introduced into the body of a father or mother, at one time or another during pregnancy, in sufficient

large dose, can cause teratogenesis. Therefore, teratogens in the narrow sense of the word should

to name only toxicants, causing effect at concentrations that do not have a significant effect on

the body of the parents. In the course of laboratory and epidemiological studies, it was found that many

xenobiotics have a fairly high potential for reproductive toxicity. Of the surveyed

about three thousand xenobiotics, about 40% have the properties of teratogens.

There are four types of fetal pathology: death, deformities, growth retardation,

functional disorders.

The action of a toxicant, accompanied by the death of the embryo, is often referred to as

embryotoxic.

3.1.1. Patterns of teratogenesis

In the course of studying teratogenesis, it was possible to identify a number of patterns, among which the main ones are:

1) toxicokinetic; 2) genetic predisposition; 3) critical periods of sensitivity;

4) commonality of formation mechanisms; 5) dose dependence.

Features of toxicokinetics. Teratogenic effects on the fetus are only substances that are well

passing through the placental barrier. Many teratogens are exposed in the mother or fetus

bioactivation (see section "Metabolism of xenobiotics").

genetic predisposition. Sensitivity to a particular teratogen is significantly

differs among representatives of different species, subspecies, and even individuals of the same species. So,

rabbits and mice are very sensitive to cortisone, which causes cleft palate in offspring. In rats

this defect is not detected under the action of the substance. The teratogenic effect of thalidomide is extremely

humans, higher primates, some lines of albino rabbits are sensitive; separate lines of rats and

mice only respond to very high doses of the substance. Most mammals are resistant to

action of the toxicant.

In part, this phenomenon is associated with significant differences in the toxicokinetics of xenobiotics.

Critical periods of sensitivity. The complex process of embryogenesis includes proliferation,

differentiation of germ cells, their migration in the developing organism and, finally, the beginning

proper organogenesis. All these phenomena must follow in a certain order and be absolutely

agreed. The first 2 weeks of the embryonic stage of human development is a period of intense cellular

proliferation. After fertilization, the cells divide rapidly, forming undifferentiated

cells are blastocytes. This is followed by periods of laying germ layers and organogenesis. Early

stage of embryonic development during the period of rapid cell proliferation (the first 2 weeks of development)

damage by toxicants, as a rule, ends with the death of the embryo.

The period of highest sensitivity to teratogens, in which they have the most significant

effect on the fetus and induce the appearance of gross morphological defects, this is the period of laying

germ layers and the beginning of organogenesis (the first 12 weeks of embryonic development). Period

organogenesis begins after the differentiation of the germ layers and ends with the formation

main organs. The period of organogenesis is followed by periods of histogenesis and functional maturation.

organs and tissues of the fetus (table 4).

Table 4. Critical periods of human embryogenesis. Examples of substances that exert pathogenic

effect on the fetus (J.V. Aranda, L. Stern, 1983)

Periods Anatomical Formations/Functions

Organogenesis

2 - 7 weeks:

eyes, brain, spinal cord, heart, arc

aorta, skull,

3 - 8 weeks:

limbs, lips

6 - 10 weeks:

urogenital system, teeth

7 - 12 weeks:

fingers, genitals, abdominal wall, palate

Thalidomide

Diphenylhydanthione

Histogenesis Alcohol

functional

maturation

External sexual characteristics;

Body weight;

Behavior

Tetracycline

The duration of the periods of intrauterine development in various species of mammals

presented in table 5.

Table 5. Duration of periods of prenatal development in different species

mammals (day). Consequences of the action of teratogens

Type of Implantation Embryonic Fetal

Consequences

prenatal

morphological defects

physiological and

functional disorders

The type of disorder caused by the substance is determined by the stage of development of the fetus and the specific time

impact. In order for a certain teratogen to cause damage to a particular organ, the fetus must be

exposed to the action of this substance during the formation of this body. For the development of various

organs "critical periods" are noted in different time after conception. Histogenesis and functional

organ development begins before the completion of the period of organogenesis and continues during the period of fetal growth.

The adverse effects of teratogens in this period are no longer morphological defects

organs and systems, but various kinds of functional disorders.

Formation mechanisms. Various substances with a different mechanism of toxicity, with

effect on the fetus in the same critical period, often cause the same types of disorders. From

It follows from this that it is not so much the mechanism of action of the toxicant that is significant, but the fact itself

damage to cellular elements at a certain stage of development of the organism, initiating in many respects

the same cascade of events leading to deformities (Figure 1)

Figure 1. Proposed stages in the formation of developmental defects under the action of toxicants on

Dose dependence of action. Most teratogens have some dose threshold, below

which the substance does not exhibit toxic properties. Apparently, the appearance of developmental defects

involves damage to a certain critical number of cells, higher than that which the embryo in

able to quickly compensate. If the number of damaged cells is below this level,

the effect of the toxicant will pass without consequences, if it is much higher, the death of the fetus will occur. This

the situation can be illustrated by the results of studies of the teratogenic activity of TCDD,

performed by Moor and collaborators (1973) (Table 6).

Table 6. The incidence of developmental defects in newborn C57BL/6 mice after

feeding pregnant females TCDD

pregnancy

Split

anomalies

double sided

kidney anomaly (%)

3.1.2. Features of the toxicokinetics of teratogens

Once in the mother's body, the substances are distributed in accordance with the toxicokinetic

xenobiotic properties. Pregnancy significantly affects the nature of the distribution (decreases

binding of toxicants by proteins, the volume of distribution increases) and the rate of excretion of substances

(the power of glomerular filtration increases) from the mother's body. Activity of enzymes I and II

phases of metabolism of foreign compounds is reduced.

The toxic effect of xenobiotics may depend on the action of their metabolites on target structures,

produced in the body of the mother and/or fetus. The main organ of bioactivation is the mother's liver.

However, highly chemically active products formed during metabolism, quickly

react with the structural elements of the liver or organs and tissues of the mother, and are unable to reach

fetal tissues. Thus, only more stable, that is, more inert

chemically, molecules formed in the mother's body, or reactive metabolites,

formed directly in the tissues of the fetus. Some substances are metabolized in the placenta.

Once in the bloodstream of the fetus, toxicants are distributed in its organs and tissues in accordance with the laws

toxicokinetics. Many of them are metabolized. It has now been established that although

the activity of cytochrome P450-dependent oxidases in embryonic tissue is significantly lower than in tissue

woman's liver, it is still sufficient for the formation of toxic metabolites. Ability

fetal hepatic tissue to the metabolism of foreign compounds is constantly changing over time. Smooth

the endoplasmic reticulum develops in the cells of the fetus by the 40th - 60th day of pregnancy. In the middle

during pregnancy, the intensity of xenobiotic metabolism by fetal tissues is 20 - 40% of

intensity in adult tissues. The experiment shows bioactivation by embryonic tissue

mice, rats, rabbits such teratogens as benzo (a) pyrene, 3-methylcholanthrene, diethylstilbestrol, 2-

dimethylaminofluorene, etc. The components of the second phase of metabolism are not equally developed in the fetus.

The level of glucuronidation is low; sulfation enzymes, conjugation with glycine and glutathione

quite active. In connection with the above, the sensitivity of the fetus to toxicants is constantly

changes.

3.1.3. Mechanisms of action of teratogens

The teratogenic effect develops under the action of a toxicant in a certain dose, on a sensitive

body, in a certain period of its formation. Many mechanisms have been identified through which

xenobiotics have an adverse effect. Understanding these mechanisms helps to anticipate

the risk associated with contact with the substance, it is correct to extrapolate the data obtained in

animal experiments on humans.

Mutation generation (mutagenesis) - the phenomenon of sequence modification by a toxicant

nucleotides in a DNA molecule (see above). It has been established that about 20 - 30% of fetal development disorders

due to mutations in the germ cells of the parents, and the mutations are inherited. Somatic mutations

fetal cells to early stages his formations are also extremely dangerous, as they change

a sufficient number of dividing cells to initiate structural and functional defects

development. A change in the hereditary code is accompanied by the synthesis of defective proteins (enzymes,

structural proteins), which in turn leads to functional disorders, often not

compatible with life.

Chromosome damage is the phenomenon of rupture of chromosomes or their fusion (non-disjunction in the process

mitosis). These violations according to modern estimates are the cause of about 3% of fetal developmental disorders.

The frequency of chromosome damage increases with maternal age. Causes of the effect, in addition to

chemical influences, there may be viral infections and the effect of ionizing radiation.

Damage to repair mechanisms. Violation of the properties of the genetic apparatus of the cell can be

a consequence of the inhibition of the activity of enzymes that provide repair spontaneously

transforming DNA molecules (hydroxyurea, folic acid antagonists).

Mitosis disorders. Mitosis is a complex cytophysiological process by which

a dividing cell passes on to daughter cells the same set of chromosomes. Many toxicants, acting

on a special cellular apparatus (cell spindle, etc.) to ensure normal mitosis,

cause violations of the process (cytosine arabinoside, colchicine, vincristine).

Violation of the biosynthesis of vital molecules can be the result of the action of toxicants.

Many substances are capable of disrupting protein synthesis, blocking replication processes (DNA synthesis),

transcription (RNA synthesis) and translation (protein synthesis itself). These substances include

many cytostatics and some antibiotics. For the most part, the action of these substances leads to the death

fetus; deformities are noted much less frequently.

Substances that make it difficult for the mother to enter the body necessary for plastic metabolism

precursor and substrate molecules are teratogens. Diet disorders - deficiency in the diet

vitamins, minerals, causes a slowdown in the growth of the fetus, its death, leads to teratogenesis. Wherein

fetal changes appear earlier than maternal health problems. The most famous example

is endemic cretinism, characterized by a slowdown in physical and mental development

in regions with low iodine content in water and soil. Deficiencies can develop with

intake of substances-analogues or antagonists of vitamins, amino acids, nucleic acids into the body

etc. Some substances block the flow necessary elements into the mother and fetus.

So, chronic intoxication with zinc is accompanied by a significant decrease in the intake of

Substances capable of inhibiting the activity of plastic metabolism enzymes in fetal cells disrupt

its development.

Violation of energy metabolism can lead to teratogenesis or fetal death. Causes

conditions can become a blockade of glycolysis, damage to the cycle of tricarboxylic acids (iodine- and fluoroacetate, 6-

aminonicotinamide), blocking the electron transport system and uncoupling the processes of oxidation and

phosphorylation (cyanides, dinitrophenol).

Damage to cell membranes. Violation of the permeability of the membranes of embryonic cells can

be accompanied by their death and impaired embryogenesis of the eyes, brain, limbs. It is believed that the basis

teratogenic effects of substances such as dimethyl sulfoxide (DMSO) and vitamin A, lies precisely this

mechanism.

Thus, almost all known mechanisms can underlie teratogenesis.

toxic action of xenobiotics (see section "Mechanisms of action").

4. Characteristics of some toxicants affecting reproductive functions

4.1. Thalidomide

Thalidomide (Figure 2) is one of the most active known human teratogens.

Figure 2. Structure of thalidomide

In the 60s, this drug was used in medical practice in Germany, Great Britain, and others.

European countries and Australia as a sedative. The substance was teratogenic

even in cases where it was used once from the third to the seventh week of pregnancy in doses

more than 0.5 - 1.0 mg / kg. The most common type of violation is fecomelia - shortening or complete absence of

limbs in newborns. More than 10,000 cases of fecomelia have been registered. As stated above,

there is a pronounced species sensitivity to the drug. So, in mice and rats, the toxic effect

does not come to light even at action in doses more than 4000 mg/kg.

This substance is a pronounced teratogen for experimental animals. For a person

this type of toxic action has not been conclusively proven. Mercury chloride causes abortion, however,

transplacental intake of inorganic mercury compounds into the fetus does not lead to

congenital anomalies. Mercury vapor, acting inhalation, causes disturbances menstrual cycle.

Elemental mercury also has the ability to cross the placental barrier. Increased

exposed to mercury amalgams.

Methylmercury causes severe damage to the fetal brain, accompanied by neuronal

degeneration and proliferation of glia, especially pronounced in the cerebellar cortex and telencephalon. Depth

violations depends on the timing of pregnancy. Especially dangerous is the effect of the toxicant in the second and third

trimester of pregnancy. Some manifestations of pathological changes are detected immediately after

birth, others after a few months. The main symptoms of the lesion are spasticity, hypotension,

microcephaly, violation of the movement of the eyeballs (nystagmus, strobism), mental retardation,

dysplasia of teeth. There are no data on the dose load leading to pathology.

4.3. Lead

The fact that the metal affects reproductive functions has been known for over 100 years. At 12 - 14 weeks

pregnancy, the substance begins to cross the placenta. At long acting on the mother's body

lead accumulates in the tissues of the fetus. The consequences of this are: abortion, premature birth,

perinatal death. There are reports of neurological disorders in children born

women whose blood lead content is more than 10 mg / dL. Data on the ability of lead to cause

there are no congenital malformations.

Lead exposure to fathers also adversely affects the development of the fetus, but not yet

it is clear whether this is a consequence of a direct effect on spermatogenesis (chromosomal aberrations, decreased

number of spermatozoa, changes in their shape and activity). It is possible that in some cases the reason

violations - damage to the mother at home with lead dust brought by the father from work.

Children exposed to lead in the womb require long and constant

monitoring their health. It is necessary to control the amount of lead in the blood plasma,

protoporphyrins in erythrocytes, evaluate neurological status.

4.4. Cadmium

In laboratory conditions, effects associated with the action of cadmium on

reproductive functions of experimental animals. The effect depends on the dose of the substance, the type

laboratory animal, exposure period. Extrapolation of data, in this regard, per person is very

difficult. Based on experimental data, it is believed that the teratogenic effect of Cd-

also that cadmium can accumulate in the placenta and cause damage to it.

Data from human studies are less convincing. Only under the action of a substance in

In high doses, damage to the testicles, teratogenesis is sometimes noted.

4.5. Polyhalogenated biphenyls (PHB)

This group of chemicals includes more than a hundred items. Connections are used in

as insulating fluids, heat exchangers, chemical additives to oils, etc. Usually,

commercial preparations are a mixture of substances, including the more toxic dibenzofurans.

In laboratory conditions, the teratogenic effect of PHB is constantly detected. There is data according to

which the intake of substances into the body of a woman during the first trimester of pregnancy at a dose of 1000

1500 parts per million, leads to congenital malformations of the fetus. In addition, it was noted:

stillbirth, intrauterine growth retardation, exophthalmos, skin hyperpigmentation,

focal calcification of the skull bones at birth. Observation of these children shows that

congenital anomalies resolve within a few years, but neurologic signs

violations remain. It is possible to damage PHB in the postnatal period, when substances enter the

body with the milk of a nursing mother. There are no data available in the literature to establish

quantitative characteristics of the considered effects in humans.

4.6. organic solvents

Under experimental conditions on laboratory animals, it is possible to identify adverse effects

solvents on reproductive function. In this regard, organic solvents are considered as

teratogens for experimental animals.

There are isolated observations when the effect of organic solvents on women in the period

pregnancy leads to a number of birth defects, including underdevelopment of the central nervous system, hare

lips and low birth weight newborns. According to other data, the effect of solvents on men

accompanied by a decrease in libido, impotence, sperm abnormalities, and in women - a violation

menstrual cycle, decreased productivity, spontaneous abortions, premature births.

None of the identified effects is strictly scientifically proven.

4.7. Cytostatics

Chemotherapy drugs for neoplasms have the properties of teratogens if their action

occurs in early pregnancy. Among the identified teratogens: alkylating agents

(bisulfan, chlorambucil, cyclophosphamide, mechlorethamine) and antimetabolites (aminopterin, azaserine,

azathioprine, azauridine, cytrabin, 5-fluorouracil, metatrexate). The risk of having a child with congenital

defects in women taking cytostatics in therapeutic doses is 1: 10 - 1: 50, in

depending on the medium used. The action of substances is manifested by spontaneous abortions,

stillbirth, high neonatal mortality. Developmental defects in children include disorders

from the side of the central nervous system, bones of the facial and cerebral skull, anomalies in the development of the kidneys and ureters,

limbs. It was noted that among nurses who gave birth to children with developmental anomalies,

the probability of contact with cytostatics is 2.6 times higher than in the group of sisters who gave birth to normal children. At

medical workers who are constantly in contact with cytostatics, in blood cells is found

increased frequency of chromosomal aberrations.

On the other hand, there is no convincing evidence of an adverse effect

cytostatics (in terms of "increased risk of teratogenesis") on the father's body before, or during, conception.

5. Identification of the effect of toxicants on reproductive function.

5.1. Experimental study

It is extremely difficult to assess the toxic effect of substances on reproductive functions, since

the mechanisms and conditions leading to an adverse effect are diverse and complex. At present

time worked out a large number of protocols of experiments in which such studies

are performed. Usually they are carried out in four stages:

1. The study of fertility and general reproduction - in experiments on one generation of animals;

2. The study of fertility and general reproduction - in experiments on several generations

animals;

3. Study of teratogenic activity of substances;

4. Identification of perinatal and postnatal toxicity.

Experiments are performed on animals kept under strictly controlled conditions.

The study of fertility and reproduction. Experiments are performed on laboratory animals,

usually rats. Usually 20 males (at each of the doses studied) are injected with the studied toxicant in

within 60 days before mating, as well as 20 females - within 14 days before mating. Temporary

the periods are selected based on the timing of the completion of the full cycle of spermatogenesis and ovulation.

After mating, the females are treated with the toxicant for the entire period of pregnancy and until

moment of cessation of lactation.

The test substance is added to feed or drinking water. Dose dependence is determined in

ranges: doses that cause threshold toxic effects in parent animals (maximum

study) - doses acting in natural conditions on a person (minimum study).

After mating, the males are sacrificed and examined; half of the females are killed in the middle of the period

gestation and examined for pre-implantation and post-implantation mortality

fetus. The other half of the females are given the opportunity to carry and feed offspring. After

at the end of the feeding period, rat pups are sacrificed and subjected to examination in order to identify

developmental defects. In control experiments, animals are mated that have not been exposed to

toxicants (only males, only females, both parents).

The severity of the toxic effect of the test substance on reproductive functions is assessed

according to the following indicators:

Preimplantation death - the number of corpus luteum in the ovaries, relative to the number of places

implantation of eggs in the uterus;

Post-implantation death - the number of sites of egg resorption in the uterus, relative

total number of implantation sites;

Morphological changes in the reproductive organs of animals;

The length of the gestation period;

The number of offspring and its condition, the ratio of live and dead newborn rats, weight

rat pups, the presence of visible deformities;

Characteristics of the development of newborns: weight gain, mortality, etc.

The presence of morphological defects in the formation of organs and tissues in rat pups after

mother feeding.

All indicators are quantified, processed statistically and compared with

controls. Significant, statistically significant violations of at least one of the assessed

indicators indicates the reproductive toxicity of the test substance.

Significantly more time-consuming is the research protocol, which involves tracing

adverse effect in several generations. The main difficulty lies in the correct

formation of the studied groups and comparison groups. With the content of such protocols, one can

get acquainted in the specialized literature.

Study of teratogenic activity. During the study, the toxicant can be administered for the entire period

pregnancy, from conception to childbirth. However, they are usually limited to studying the consequences of an action.

substances during the period of greatest sensitivity of the fetus - the period of organogenesis. Experiments are performed as

as a rule, on rodents, more often rats. The method of administration and dose of the toxicant are similar to those described above.

The most typical protocol form is shown in Table 7.

Table 7. Typical protocol for testing teratogenic activity and perinatal/postnatal

toxicity

TERATOGENESIS

PAIRING

BEARING

Females are injected with a toxicant during the 6th - 15th day of pregnancy.

Mother and offspring are sacrificed on the 20th day

PERINATAL/POST-NATAL TOXICITY

PAIRING

BEARING

For females, starting from day 15

pregnancy, injected with a toxicant

LACTATION

The introduction of a toxicant to

completion of lactation (21 days).

Killing mother and offspring

In the course of the study, structural disturbances in the development of the fetus are evaluated (Table 8), the value

embryo-fetal mortality.

Table 8. Some of the developmental anomalies identified during the evaluation of xenobiotic teratogenicity

A. Defects detected during general inspection

1. Skull, brain and spinal cord

Encephalocele - protrusion of the brain through defects in the bones of the skull

Exencephaly - lack of skull bones

Microcephaly - small head size

Hydrocephalus - enlarged brain ventricles

Spina bifida - nonunion of the vertebral arches

Enlarged nasal passages

No nasal septum

Microphthalmia - small eyes

Anophthalmia - absence of eyes

Lack of eyelids

4. Jaws

Micrognathia - small size of the lower jaw

Agnathia - absence of the lower jaw

Aglossia - lack of language

Astomia - absence of a mouth opening

cleft lip

split sky

6. Limbs

Micromelia - shortening of the limbs

Hemimelia - absence of separate limb bones

Phocomelia - the absence of all long bones of the limbs

B. Defects of internal organs

1. Intestine

Umbilical hernia

Ectopia of the intestine - extrusion of the intestine outside the abdominal cavity

Dextrocardia - the location of the heart in the right side of the chest cavity

Lung enlargement

Reducing the size of the lungs

Hydronephrosis - kidneys are enlarged, filled with fluid

Agenesis - absence of one or both kidneys

Violation of the shape of the organ

B. Skeletal disorders

Polydactyly - having extra fingers

Syndactyly - fusion of fingers

Oligodactyly - the absence of one or more fingers

Brachydactyly - short fingers

Additional ribs

fused ribs

Rib branching

tail shortening

No tail

tail shape disorder

Since almost all detected disorders occur in intact animals, and can also

be caused by factors of a non-chemical nature, much attention must be paid to the formation

representative control groups and statistical processing of the results.

As an addition to the proposed protocol, the possibility of using

methods for assessing the functional state of animals born from females exposed to

the chemical under investigation. Postnatal assessment of the functional state of animals

includes determining the growth rate, the state of the kidneys, liver, cardiovascular, respiratory

systems, CNS.

Study of perinatal and postnatal toxicity. The study is performed on pregnant women

female white rats (table 7). 20 animals (per study dose) treated with study drug

during the last third of pregnancy and lactation. Methods of administration and doses tested

substances are selected according to general rules(see above). Assess the duration of pregnancy, the number and

size of newborns, growth rate of offspring, etc. It is advisable to use morphological and

physiological methods for assessing the health status of rat pups. The results are processed statistically and

compared with controls.

The establishment of the teratogenicity of a number of toxicants gives rise to the idea that the main cause

developmental defects are production factors and environmental factors. Actually

this is not true. A real assessment of the potential danger of a toxicant for humans is a difficult task. Although in

experiments on animals, a lot of work has been done to identify teratogens, mutagens, substances

disrupting reproductive function, it is not possible to fully transfer the obtained data to a person

seems possible. Such a transfer is impossible due to a number of circumstances: differences in

the structure of the genome in representatives of species of laboratory animals and humans; sensitivity differences

developing tissues to individual toxicants; interspecies differences in the toxicokinetics of xenobiotics,

including metabolic features (this is important because different species may form

different metabolites of the same toxicant, the time

parameters of action of substances); the difference in physiological mechanisms for the implementation of reproductive

functions, duration of individual periods of fetal development, etc.

5.2. Lesion risk assessment

Theoretically, it is possible to assess the risk of impaired reproductive function only taking into account the dose

loads of xenobiotic, since, as mentioned above, there are practically no substances that are safe for

under any conditions of exposure and in any doses. However, in practice, to do this in relation to a person in

currently not possible. Extremely complex data acquisition methodology

for building "dose-effect" dependencies, in relation to the problem under consideration, does not allow

gather the information needed for this.

In this regard, the assessment of the risk of damage and the diagnosis of the effect of the toxicant on the reproductive function

people are based on a comprehensive study of the state of health, specific circumstances of life and work

examined.

Signs of reproductive dysfunction may vary, but should always be taken under

control of any identified case. It is possible, in particular, to consult a doctor about obtaining

information about the dangers of certain toxicants that the father or mother has to deal with

in production. At the same time, the employee may complain about the state of health, which, according to him

opinion, indicates the harmful effect of a certain substance (substances). Quite often for advice

turn barren married couples, with a request to decide whether this or that is the cause of their misfortune

other toxicant with which one or both spouses are in contact. Finally, the reason for the study may

be asking parents to advise them about possible reasons developmental defect in their child.

In all such cases, the doctor needs to examine the patient, document all

complaints, identify the sequence of symptoms, their severity,

duration. It is advisable to interrogate, and, if necessary, examine the patient's colleagues for

the subject of revealing similar manifestations in them. Attention should be paid to the possibility

on a woman "non-industrial toxicants" in everyday life (solvents, detergents, cosmetics,

bad habits, medication, etc.). Important information for decision making is information about

age, profession of patients, previous diseases.

Retrospective assessment of possible toxic effects is not always a solvable task,

since the information presented by patients, as a rule, is subjective. Persons with

reproductive function is much more likely to remember the fact of the impact of "harmfulness" than

face without one. Identification of the time of exposure to the toxicant and the establishment in what period

pregnancy, this happened is also based, as a rule, on a survey, and therefore it is very difficult.

When studying the working conditions of the surveyed, it is necessary to pay attention to the list of potentially

hazardous active toxicants, their quantitative characteristics at the workplace, accepted

protection measures (technical, organizational, etc.).

It is important to establish the absence of genetic defects in the parents and relatives of the subjects.

The most common "spontaneous" disorders in humans are: anencephaly, spina bifida,

limb defects, cleft palate, cleft lip, congenital hip dislocation, pyloric stenosis.

Medical examination of an exposed (exposed) pregnant woman

toxicants, should be thorough and include a study of the condition of the fetus, especially its

mobility, heart rate, size.

The best way to estimate the amount of a toxicant affected is to determine whether it is itself or

metabolites in the biological media of the mother's body (blood, urine), biological markers of action

toxicants (enzyme activity, blood picture, content of biologically active substances, etc.).

Useful methods for assessing a man's reproductive functions are: body weight, testicular size,

semen analysis (sperm count, motility, morphology), endocrine functions

(follicle-stimulating, luteinizing hormones, testosterone, gonadotropin). On examination

women evaluate: body weight, endocrine functions (gonadotropin, prolactin, choroid gonadotropin,

estrogen, progesterone), cytological properties of the cervical fluid, anatomical and morphological

features of the organs of the reproductive system. In some cases, there is a need for prenatal

fetal examinations (ultrasound diagnostics, radiation diagnostics, fetoscopy, fetography,

amniography, amniocentesis, chorion examination, fetal blood analysis, skin and liver biopsy

5.3. Epidemiology of toxic action

5.3.1. Analyzed indicators

Adverse effects of chemicals on human reproductive function, as well as the frequency

and the prevalence of disorders and defects in the development of the fetus and child caused by toxicants,

studied by epidemiological methods. In such studies, quantitative data

obtained through special methods.

One of the frequently evaluated indicators is fertility, i.e., the characteristic

a woman's ability to become pregnant. Fertility characterizes preimplantation

processes (see above) and does not allow distinguishing the toxic effects of substances on the reproductive systems

men and women. Another indicator that can be measured is gestation.

Bearing is determined by the ability to bear a viable fetus and is also a general

characteristics of reproductive functions in the population. This indicator does not distinguish between toxic

lesions of men and women, normal and pathological births, does not take into account preterm birth

or death of the child after childbirth. The term pregnancy refers to the period of gestation before childbirth.

(38 - 40 weeks) and characterizes the post-implantation period of fetal development.

Fertility and gestation (the so-called intensive characteristics

reproduction) are not exhaustive indicators in assessing adverse effects

reproductive toxicants. Not always easy enough to diagnose

pregnancy in early dates and even more so to state the fact of conception, which affects the correctness

evaluated indicators. Establishing the fact of fetal loss depends on the correctness of the establishment

pregnancy. Any upward trend in the number of abortions should be assessed against the number

spontaneous miscarriages, the frequency of which under "normal" conditions is 20 - 56%. Estimated

the probability of spontaneous abortion at different stages of pregnancy is presented in table 9.

One of the most common causes of abortion is the formation of chromosomal abnormalities in the fetus.

Table 9. Probability of spontaneous abortions at different stages of pregnancy

Time after Probability of abortion Time after Probability of abortion

ovulation (%) ovulation (%)

14 - 20 days

3 - 5 weeks

6 - 9 weeks

10 - 13 weeks

14 - 17 weeks

18 - 21 weeks

22 - 25 weeks

26 - 29 weeks

30 - 37 weeks

38+ weeks

The third frequently assessed indicator is the frequency of defects in the development of the fetus and child. These

defects can be detected immediately after birth or after a sufficient time after birth. Defects

can be anatomical, physiological (metabolic disorders) and behavioral. Defects

human development - frequent occurrence. Separate types of violations are detected in 5-15% of all cases.

childbirth. In 2% of cases, the changes are so pronounced that they require special treatment. Most often

developmental defects are identified auricles, atypical pigmentation skin. In general, the frequency

developmental defects is an unreliable characterization of the teratogenic potential of a toxicant. The fact is that

defects associated with the action of xenobiotics are quite rare and therefore statistically

insignificant. In most cases, the causes of defects remain unexplained (Table 10).

Table 10. Causes of fetal defects in humans

Unknown 65 - 70%

Genetic defects 20%

Toxicants 4 - 6%

Chromosomal disorders 3 - 5%

Maternal infection 2 - 3%

Metabolic disorders

mother 1 - 2%

Pathological reactions

mother up to 1%

The overall assessment of the reproductive toxicity of substances to humans is extremely complex. Even

the result of acute exposure to a toxicant manifests itself in this case after a long time, sometimes

years. It is difficult to study the effect of toxicants even on gametes. So, to evaluate the effect of a toxicant on

spermatogenesis is possible only after the maturation of spermatozoa and their ejaculation, and this process

stretches out over months. In addition, violations may be the result of long-term action of the substance in

small doses, but manifest poorly detected functional changes, such as menopause,

change in sexual behavior.

5.3.2. Information collection methods

There are several data collection methods to assess the influence of chemical factors.

environment on human reproductive function. In particular, correlation

studies among several population groups with different levels of exposure to xenobiotics according to

indicator "frequency of violations of reproductive function". The results are seen as

evidence of the teratogenicity of a substance, if in a group with a higher level of xenobiotic

load is determined by a higher frequency of defects in reproductive function. Research

of this type are retrospective and prospective (see the section "Epidemiological methods

research").

In the course of retrospective studies, comparison groups are formed, in one of which, in

surveyed, revealed violations of reproduction, in the other - healthy people are represented. Further

the extent to which the assessed factor influenced the representatives of these groups is studied. If

the intensity of the impact of the factor on representatives of the risk group is significantly higher (by frequency,

duration, dose), a presumptive conclusion is made about the possible presence of a toxicant

teratogenic properties. The disadvantage of the study is the element of subjectivity introduced into the method

the fact that the formation of groups, including control, is carried out by the researcher.

Prospective studies involve comparative examination of individuals who have had contact with

assessed factor and persons who did not have such contact (it is possible to compare people who had

various degrees of exposure), in terms of the presence of adverse changes in their reproductive

functions. During the study, the state of the study and control groups is assessed for a certain

time period. The factor is considered as significantly acting if the defects in the reproductive

functions are detected much more often in the risk group. If the formation of groups occurs randomly

Thus, the study is called randomized. Results of randomized trials

less subjective. However, they also have disadvantages. For example, not always

it is possible to fully identify rare violations in groups.

Interventional studies are designed to establish the frequency of development of the studied

violations in the control group (those exposed to the toxicant) and the group of persons in relation to

who have taken preventive or curative measures. If in the control group violations

are more common, preliminary conclusions are made about the etiological significance of the substance.

The basis for conducting a thorough study of the teratogenicity of a substance is often

reports of adverse effects of its action identified during routine surveys.

Such reports themselves cannot be considered as evidence of the harmful effects of a xenobiotic,

because they are based largely on the subjective assessment of a specialist. Accepting a hypothesis as a fact

only on the basis of special systematic studies.

5.3.3. Control of teratogenesis in a population

An important element of the activity of the medical service is the control of teratogenic effects

xenobiotics in human populations. This control can be carried out according to

programs that meet the criteria developed.

Relevance. The developmental defects considered must be clinically significant. small

violations of the morphology of the face, limbs, etc. may be signs of

teratogenic effect of new xenobiotics. Multiple developmental defects represent a special

interest, since many known teratogens cause a complex of disorders.

Temporal correctness. Most deformities are the result of the action of xenobiotics on

fetus in the first 2 - 4 months of pregnancy and therefore are detected only after 5 - 9 months (after birth).

In case of violation of the functions of internal organs, the development of the central nervous system, behavioral defects, then their

diagnosis may occur much later. This requires assessing the state of not only

newborns, but also older children.

Sensitivity. The proposed survey methods should be sufficiently sensitive

to identify moderate increase the frequency of occurrence of defects (two or less times). For

comparison of the information received, data on the magnitude of the studied indicators in other

regions or in a given region until the time of the survey. Such data should be accumulated within

long enough and include information subject to quantitative methods

comparisons. A randomly detected increase in the frequency of malformations in a population occurs more often

the smaller the statistics of previous observations.

Detectability of the reasons for the increase in the frequency of developmental disorders. Increasing number of violations

development may result from:

Changes in the composition of the population (age composition, socio-economic status);

Changing the methodology for identifying developmental defects;

The appearance in the environment of teratogenic factors.

An important condition for the truth of the judgment about the increase in the indicator under study is detailed

analysis of real cases. If it is possible to detect a lower frequency of developmental defects in the examined

population (compared to normal), then the reasons for this should be identified. Sometimes it can help

improving the methods of carrying out preventive measures in society as a whole.

The ability to identify multifactorial effects. Most fetal defects

multifactorial in nature. In this regard, it must be taken into account that the combined effect

several mutagenic factors, may be accompanied by the formation of a pattern of deformities that are not characteristic

for each of the active agents. Working in such conditions, it is sometimes difficult to establish the real

reason for violations. At the same time, a sharp rise in the level of detected defects in the population is faster

indicates the only reason for the observed phenomenon.

Comparability is the property of the methodology used in a survey to present data that

which can be compared with results obtained from other sources or information centres,

is one of the most important research requirements. Accuracy in the description and diagnosis of detected

violations is largely determined by the qualifications of specialists involved in the survey. V

Currently, one has to face the fact that various sources (conclusions of pathologists,

pediatric and surgical clinics consultations) typically represent data collected from

varying degrees of sophistication and depth.

Price. The cost of the survey is mainly determined by the number of people covered by the survey.

contingent and the cost of material equipment. When planning work, you need to focus on

financial capacity so that the study can be completed.

Even during fetal development, all organ systems, including the reproductive one, are laid in the fetus. It turns out that the child has not yet been born, and his health in terms of reproduction is either quite good, or has already received its share of the negative impact.

Reproductive health is a component general condition organism. It turns out that it directly depends on the lifestyle of the mother during pregnancy, as well as on the health of the father.

The concept of reproductive health

This term is directly related to demographic science, which studies the level of mortality and fertility in society. But reproductive health- it's a part general health human, which implies physical, spiritual and social well-being.

If we talk about health, then we mean not only the absence of diseases in the reproductive system, dysfunctions, but also state of mind and public welfare.

Currently, reproductive health is taken care of not only by doctors, but also by psychologists and sociologists.

Statistical data

Statistics are stubborn things, and they have been increasingly disappointing in recent years. Ours leads the wrong way of life, and in some cases heredity is not very good, so a large percentage of young people risk joining the army of the childless.

The reproductive health of adolescents leaves much to be desired. Factors that adversely affect it include:

• early start sexual life;
• a large percentage of diseases that are sexually transmitted;
• a huge number of young people who drink alcohol and smoke.

All this leads to the fact that still very young girls come to have an abortion, and this cannot but affect their reproductive health. It leads to various diseases in the reproductive system, disorders monthly cycle. The trouble is that young people at the first symptoms of the disease are in no hurry to see a doctor, hoping that everything will soon normalize by itself.

Now a large number of children are already born with certain pathologies, and then what can we say about their health when they approach the age when it is time to start a family and give birth to children?

According to statistics, at the beginning family life almost every second person has chronic diseases that can directly or indirectly affect a person's reproductive health.

That is why this issue has recently been of such concern not only medical workers but also the whole society. Healthy children are our future, and how can they be born as such when their future parents cannot boast of their reproductive health?

Conditions for maintaining reproductive health

Reproductive health of a person and society are closely interconnected. The question arises, what can be done so that the future generation is born healthy and able to give birth to the same healthy children? If you carefully study the recommendations, then there is nothing impossible in them:

Rules that anyone can follow, but, unfortunately, not everyone thinks about it. And the reproductive health of adolescents will certainly affect their condition during adult life on the health and well-being of their children.

The direct duty of parents is to constantly educate girls and boys in these matters.

Vitamins for the reproductive sphere

Everyone has long known that without vitamins, a person begins to have problems in the work of internal organs and systems. Many of the vitamins and microelements have the most direct impact on the reproductive health of the population.

Among them, the following are worth noting:

1. Vitamin A is involved in the synthesis of an intermediate product of sex hormones. With its lack in the diet of the male population, the process of formation of spermatozoa is disrupted, and even infertility can develop in women.
2. Vitamin E in not enough causes a decrease in the formation of seminal fluid in men, and in women, pregnancy can be interrupted at different times.
3. Vitamin C is almost universal, it affects the functioning of many organ systems. Admission to large doses of this vitamin even allows you to get rid of some varieties male infertility.
4. Folic acid is essential for proper development baby in the womb. Its deficiency in the body of a woman before pregnancy and in the first months of bearing a child leads to the development of birth defects in the nervous system of the baby.
5. Iodine is needed for normal operation thyroid gland, without which the proper functioning of the reproductive system is simply impossible. If a woman is sorely lacking this element during pregnancy, then there is a high probability that the child will be born with a diagnosis of cretinism.

You can talk a lot about other vitamins and minerals, but there should be only one conclusion, reproductive health is one of the important components of a person's overall health. What it will be depends largely on our nutrition.

Women's health

A woman's reproductive health begins to take shape in the womb. When a girl develops in her stomach, then at this moment the formation of future germ cells occurs. How many of them will be formed during this period, so many will then mature during reproductive period woman's life.

It turns out that the expectant mother is responsible for the formation of her daughter's reproductive system. After birth and in adulthood, each representative of the fair sex herself may well affect her health, including reproductive health, positively or negatively.

From the early childhood it is necessary with mother's milk to educate and instill in girls the right basics hygiene and personal care. Sometimes mothers do not pay due attention to this issue, hence the large number of diseases of the genital and excretory spheres in very young girls.

Primacy among such problems is occupied by inflammatory diseases of the reproductive system. If left untreated, they go into chronic form and can significantly affect a woman's reproductive health in the future.

It is probably not worth talking about the prevention of early abortions, especially the first ones, which can put an end to future motherhood once and for all.

Components of reproductive health

They affect our body throughout life. Already being born, a child receives from his parents at the genetic level some indicators of health, metabolic characteristics, a predisposition to certain problems.

In the first years of a baby's life, care for health, including reproductive health, falls on the shoulders of the parents. They should lay the foundation healthy lifestyle the life of the child and explain the importance of this for the health of his future children.

For some reason, it is customary to talk more about women's reproductive health, although in recent years it has been found that men in 50% of cases are also responsible for the absence of children in the family.

Diseases and reproductive function

Currently, there is a huge list of diseases that adversely affect the reproductive health of the family.

1. Infectious diseases. Among them are those that can lead to infertility, such as chicken pox, mumps, especially in boys. There is no need to talk about venereal infections at all.
2. General somatic diseases. Problems with cardiovascular system, kidneys, liver, diabetes can not only worsen the condition of the body, but also disrupt the hormonal background, and this cannot but affect reproductive health.
3. congenital diseases. Many doctors are convinced that in most cases infertility originates from early childhood. And this applies to both boys and girls.
4. Reception medicines. Some have a fairly strong effect on reproductive function. These include:

• corticosteroids;
• anticonvulsant drugs;
• antidepressants;
• tranquilizers;
• neuroleptics.

Of course, in some situations, these drugs simply cannot be dispensed with, but it is always necessary to evaluate the health risk, especially if you are still going to have children.

External environment and reproductive health

Reproductive health is not only the state of the human sexual sphere, but also general well-being, which is not always at a high level. A large number have the most direct impact on reproductive function.

It will not be possible to completely get rid of such an impact, but everyone is able to change the situation for the better and to some extent eliminate or reduce the impact of negative factors.

Risk factors for reproductive health

In scientific circles, there have long been various studies on the influence of factors on the health of pregnant women and, in general, on the female sex in reproductive age. In the course of long-term observations, several groups of factors were identified:

1. Socio-psychological. This is the effect of stress, nervous tension and feelings of anxiety and fear.
2. Genetic. The presence or absence of mutations in germ cells.
3. Professional. If your professional activity associated with harmful hazardous substances or types of work, it is necessary with the onset of pregnancy, and preferably even before planning it, to exclude the influence of such factors.
4. Ecological. We can influence these factors least of all, well, if only we move to a more favorable area in terms of ecology.

Consequences of poor reproductive health

Any doctor will confirm that the characteristics of reproductive health in recent years have left much to be desired. The following examples prove this:

1. Most of the population childbearing age suffering from various infectious and inflammatory diseases.
2. The reproductive health of both men and women is deteriorating sharply.
3. The number of infertile marriages is growing every year.
4. does not decrease, but, on the contrary, increases.
5. A large number of children are born with genetic diseases.
6. Oncology is becoming the scourge of our society, and a huge number of patients belong to the younger generation.
7. The nation's gene pool is rapidly depleted.

What other evidence is needed to understand that something needs to be done to strengthen and improve the reproductive health, especially of young people.

Protection of the reproductive health of the population

The concept of protection includes a large number of methods, procedures and services that can support the reproductive health of young families and each individual. V modern conditions security issues are of great importance and relevance.

More prevention work needed various diseases, especially those that affect the sexual sphere. Education must begin in the family and continue in educational institutions. This needs to be discussed with the next generation. A special role should be given to:

1. Prevention of abortion, especially at an early age.
2. Protection from infection with various infections that are sexually transmitted.
3. Consider family planning and childbearing. It is necessary to prepare for this, and the first step may be a visit to a genetic consultation, where specialists will help to calculate the probability of having children with various pathologies.

Despite the not very favorable environmental situation, the reproductive health of a person depends to a greater extent on himself. It is up to you, no one will do it for you. Remember about your children and future grandchildren, their health also depends on your lifestyle.

All these aspects are important not only for the state, but also for every person. In many ways, the possibility of procreation depends on the person himself, as well as on the foundations of his family. The state is not able to force people to live according to clear canons, so the birth of future offspring is considered by individual parameters.

General Criteria

Features of childbearing functions suggest criteria by which the body's ability to conceive or fully bear a fetus is assessed. Similar aspects have been noted medical specialists who have been observing fertility statistics for many years.

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• Deterioration of the general condition of the body.
• Deviation from the norm in biological indicators organism.
• Violation of the functionality of organs and systems.
• The presence of genetic abnormalities.
• The development of tumors in the reproductive system of organs.

The demographic situation largely depends on the fact that people avoid visiting medical institutions, not realizing how important health problems are for procreation. To increase the birth rate, it is necessary to create norms of human behavior that will prioritize a healthy lifestyle and taking care of your body. The concept of "reproductive health" today is not even known to many.

Factors affecting RZCH

Features of reproductive functions are that diseases can have a negative impact on them different nature and external environment. There are also risk factors involved. It should be noted that all these causes may have different effects in each individual case.

Diseases

There are many diseases that can negatively affect the ability to give birth (conceive) a child. Some types of diseases lead to the fact that the organs of the reproductive system suffer.

1. Infectious. dangerous diseases infectious nature leading to infertility are mumps, chickenpox and others. The features of these infections are to change a number of genes that lead to infertility. These diseases are most dangerous for boys.
2. Somatic (general). If the vital internal organs function incorrectly, then a change in the hormonal background occurs, which accordingly affects the RZCH.
3. Congenital. Infertility can be congenital if in the womb the fetus was exposed to any negative impact, as a result of which his organs may not work properly. Failure can also occur at the time of embryo formation.
4. The action of medicines. Many drugs have a strong effect on the functionality of the reproductive system. Therefore, tranquilizers, corticosteroids, antidepressants, antipsychotics and anticonvulsants are prescribed only in extreme cases. Children such drugs are contraindicated.

Attention to the state of the body, including prevention and timely treatment can significantly reduce the risk of infertility. It must be borne in mind that aspects of the normal functioning of the body are the basis of reproductive capabilities.

External environment

For the general condition of the body and, accordingly, reproductive functions, the external environment is of great importance. By itself, the external environment is not a reason for changes, as a result of which reproductive organs stop functioning. The decisive factor is a weakened organism, easily amenable to negative influence.

In recent years, cases of diagnosing tumor formations (cysts, fibroids, and others) in young girls and women have become more frequent, which, if left untreated, lead to infertility. Features of the increase in the number of patients are the influence of external causes.

Risk factors

According to statistics, women are the most likely to suffer from infertility. What are the features of the female body, scientists are studying different countries. According to the results of the research, risk factors were identified that are the cause of infertility or abnormalities during pregnancy.

Features of risk factors are that the impact on the body is gradual. In order to restore the functionality of the reproductive organs, it is necessary to exclude any kind of negative influence and undergo treatment.

The reproductive health of each person and the entire society as a whole is one whole. In order to correct the situation, it is necessary that all people be familiar with the memo, which is the key to the continuation of the human race.

1. In order to reduce the number of abortions, in the absence of a desire to become pregnant, one should be protected.
2. Any disease must be treated.
3. It is necessary to regularly carry out the prevention of diseases of the genital organs.
4. Sexually transmitted infections should be treated promptly.
5. It is better to prepare for pregnancy several months in advance.
6. You need to lead a healthy lifestyle.
7. Constantly strengthen the immune system.
8. Observe the rules of personal hygiene.
9. Eliminate bad habits.

In order for reproductive functions not to be impaired, it is very important to explain all the features of behavior even in childhood. If a responsible attitude to health is laid down from an early age, there will be no problems with the birth of healthy children.

Considering the problem of the presence of adverse factors affecting reproductive health, it should be noted that the reproductive potential of future parents begins to form from birth, especially of a girl, who must be considered as a potential mother. Therefore, maintaining health from childhood, strengthening it in adolescence among young people entering reproductive age is one of the key problems in the birth of a healthy generation.

It is impossible to overestimate the importance of a healthy lifestyle, as a style of behavior actively chosen by a person, including rational nutrition, motor activity, hygiene skills, correct mode work and leisure, culture sexual relations, no bad habits, medical activity. The number of publications on these issues is almost boundless, and it is not advisable to consider each of its aspects in detail in this paper.

Unfortunately, it should be noted that the majority of Russians still tend to have a consumerist attitude towards their own health. An unbalanced diet, primarily a deficiency of protein foods, a significant restriction of the diet, can lead to a disorder menstrual function and even anovulation in girls and disorder of spermatogenesis in boys. Insufficient physical activity in combination with high “hypodynamic” school and extracurricular workloads, it also does not contribute to preparing the girl for future pregnancy and delivery, and will not make the young man a “superproducer” in the future. But this is practically not taken into account by parents, the maximum that is remembered is about posture and problem teeth. In Russia, there are few truly healthy or at least "practically healthy" citizens, but it is almost impossible to meet a person in a medical institution who wants to know the current state of his health in the absence of subjective morbid manifestations.

On a positive note, more and more attention has been paid to differentiated approach to the sexuality education of children and adolescents. Since the interest in sex in children arises from early age(they start asking the first questions in this area at 3-5 years old), sex education should begin from the period of the first questions and last as long as the child needs it. Moreover, sexual education, which concerns the relationship between the sexes in the broadest sense of the word, is most productive in the family. Meanwhile, the success of sexual education is possible only with a complex impact on the child. Until now, the problems remain the lack of literacy of the parents themselves, the lack of practice of applying to psychologists among the population and the small number of school teachers who are ready to discuss the problems of sex with students. We are still far from the practice of foreign countries, where sex education lessons begin in elementary grades and continue for several years.

V teenage years The person is hypersexual. The formation of organs of the reproductive sphere and their functioning often outstrips the development of intelligence, and group forms of behavior with insufficient formation of moral and ethical standards, lack of understanding of responsibility for their actions can provoke an early onset of sexual activity with a random change of sexual partners (adolescent promiscuity), which most often leads to to persistent circulation in adolescent groups of STDs and unwanted pregnancy in immature girls.

This is especially important, because with an early entry into sexual life, the consequences for the girl's body can be extremely negative. Adolescent girls enter the reproductive process often anatomically and physiologically immature, socially unadapted, which significantly reduces the health of mothers and newborns. Moreover, the reproductive health of adolescent girls is currently assessed as extremely unsatisfactory. The morbidity rates of girls are 10-15 higher than those of boys. Disorders of menstrual function increased by almost 2 times, 1.3 times - the frequency of diseases inflammatory nature. Teenage girls, upon entering the reproductive process, have a very high index of infectious diseases, including 62.6% of cases - sexually transmitted diseases (2.2% - syphilis), 65.7% have extragenital pathology of the respiratory system, gastrointestinal tract, liver, kidneys, in 52.4% - gynecological diseases(colpitis, cervical erosion, chronic inflammation appendages), every sixth observed a violation of the menstrual cycle.

When examining 1000 adolescent girls (10-20 years old) who entered into the childbearing process, most of whom (84.3%) were in a registered or civil marriage, and 1000 women of a favorable reproductive age(20-24 years old), the number of unmarried women was only 7.5%, and the health status of their newborns was revealed as follows. Complicated course of childbirth was noted in 80.4% of young women in labor. Slightly more often than in the comparison group, rhodostimulation was used, it was noted clinically narrow pelvis in childbirth. In young puerperas, hypotonic bleeding was significantly more common and in early postpartum period a manual examination of the uterine cavity was performed. Only 0.6% of adolescent girls abandoned a child in the maternity hospital (all of them were not married, half of them used drugs).

In the group of young women in labor, 60 children (6.0%) were born with nicotine intoxication, 7 newborns (0.7%) were in a state of drug addiction. Since the state of newborns is associated with the reproductive health of the mother, a method has been developed for screening the reproductive health of adolescent girls, with which it is possible to assess the degree of its violation, which makes it possible to intensify activities and concentrate the efforts of doctors, social workers, teachers, parents on solving the problems of each particular teenage girl and thereby ensure perinatal protection of the fetus.

An even bigger problem than the physical and mental load delivery at a young age, is the termination of pregnancy. According to the Krasnoyarsk Family Planning Center, the number of abortions per thousand adolescents in 2002 was 54.8, and among adolescent girls who gave birth to a child, every fifth had an abortion in history, 4.2% had 2-3 abortions. Abortion is a serious endocrine stress for a woman's body, requires hormonal rehabilitation, leads to reproductive problems: inflammatory diseases, infertility, menstrual disorders, the formation of hormone-dependent diseases (myomas, endometriosis, ovarian cysts, breast pathology), most of which are background in the development of oncological pathology.

Competent prevention of unwanted pregnancy (contraception). Currently, there are many ways to prevent conception - contraception. A large arsenal of modern contraceptive means and methods, unfortunately, is not used so often, which is primarily due to the lack of sexual education and the unwillingness to turn to a specialist on such “shameful” (in the understanding of the Russian layman) questions.

Since the desire of men when choosing methods of contraception is taken into account by most women, it is interesting to study the nature and characteristics of contraceptive behavior and awareness of adolescent boys and men (age 15-45 years) on these issues - urban residents, conducted in a number of territories. Russian Federation. It turned out that the current abundance of contraceptives for women reduced the liability sexual partner for the consequences of intimacy. Despite the fact that the majority of the men surveyed (81.5%) are aware of contraceptives (80.6% named the condom, 59.9% - the IUD, 49.6% - hormonal contraception), 43.6% of men do not discuss at all, 51.2% do not consult with a woman in matters of protection against unwanted pregnancy, and only 4.9% of men would like to take on the solution of contraceptive problems.

Although among the men surveyed, 65.2% use contraceptives Unfortunately, only 18% of adolescents use methods and means of contraception, while in others age groups- about 80% of men, regardless of marital status.

Unfortunately, despite the fact that women in Russia have begun to actively use modern methods of contraception (at the end of the 90s of the twentieth century, only 19% of Russian women used them, although even in developing countries this figure reached 79%), to date, abortion , according to experts, remains their “preferred” means of birth control. Since a woman can find out about the onset of pregnancy more or less reliably by the absence of another menstrual bleeding, and sometimes such a thought comes to her even later, there is practically no choice but to artificially interrupt gestation.

Termination of pregnancy - abortion. Russia is the country that was the first to allow (in 1920) the production of abortions, and the undoubted leader in terms of their number in the present. In accordance with modern legislation RF every woman has the right to independently decide the issue of motherhood. A significant part of men and women are aware of the dangers of abortion. The circumstance provoking the decision to terminate a pregnancy, in some cases, is the social norm, which dictates that the best age for having children is from 20 to 30, in extreme cases up to 40 years. If this happens sooner or later, then the mothers themselves perceive their parenthood as a deviation from the “correct” behavior and often take extreme measures. At the moment, public and state support for a woman mother is minimal, motherhood has become almost completely her personal affair, carried out at her own peril and risk. Only the introduction of a social and legislative policy that implies real, including psychological, assistance to those mothers who would like to keep the pregnancy, could change the decision taken not in favor of the child. Moreover, in the future, infertility in marriage can become a real tragedy and the cause of most divorces. Barren marriage. The problem of infertility is quite serious, but its purposeful study began only in the twentieth century. Standards World Organization health care distinguish 21 factors of female and 19 factors of male infertility. It has been established that 75% of infertility in marriage is due to chronic inflammatory processes in the genitals caused by protozoa (trichomoniasis), bacterial microflora (streptococci, staphylococci, E. coli), chlamydia, as well as poorly treated sexually transmitted diseases. Only when integrated approach to the problem of prevention and treatment of infertility, positive changes are possible, since with the elimination of the identified causes of infertility and the prevention of diseases that serve as medical indications for abortion, one could expect an increase overall indicator birth rate within 7%, and with the elimination of secondary post-abortion infertility - up to 30%. Sexually transmitted diseases. Venereal diseases are one of the serious social and psychological problems of our time. Their social significance is determined by their high prevalence, the severity of the consequences for the health of the sick, the danger to society, and the impact on the reproduction of offspring. According to WHO, syphilis, gonorrhea, chlamydia are the most common diseases in the world, with the exception of influenza during an epidemic and malaria. About 200 million patients with gonorrhea, 250 million with chlamydia and 50 million with syphilis are registered annually in the world. Thus, for young people, the main adverse factors factors that affect reproductive health can be called, firstly, the early onset of sexual activity in adolescents, which is accompanied by their perception of sexual life in a simplified form, when up to 82% of boys and up to 45% of girls do not associate sex life with love and marriage , secondly, self-treatment and untimely treatment for medical institutions, which are the result of a low sanitary and hygienic culture of young people and a psychologically incorrect model of STD prevention built on intimidation. In addition, low awareness of health-saving behavior in the sphere of sexual relations plays a negative role.

Smoking. Great harm the whole body can cause such a harmful phenomenon as smoking. The main active agent of tobacco is nicotine. It's a narcotic poison. The smoke generated during the combustion (smoldering) of tobacco contains not only nicotine, but also a number of other substances that are harmful to the human body. These include ammonia, carbon monoxide, hydrocyanic acid, resinous substances, etc. During each puff of smoke when smoking, it comes into direct contact with the mucous membranes of the mouth and nasopharynx, bronchi and lungs. At the same time, the substances that make up tobacco smoke quickly penetrate the bloodstream and reach all human organs and tissues.

Exclusively bad influence smoking affects the respiratory, digestive, cardiovascular and nervous systems. Tobacco smoke, getting into the mouth, irritates the mucous membrane, reduces the sense of smell, taste sensations destroys tooth enamel.

According to the World Health Organization, angina pectoris and myocardial infarction occur in heavy smokers 12-13 times more often than non-smokers, stomach ulcers 10 times more often, etc.

A regular increase in the risk of congenital malformations was established with an increase in the number of cigarettes smoked by a woman daily, especially during the 3rd month of pregnancy. Swedish scientists Erickson, Kellen and Westerholm revealed a significant predominance of smokers in the group of women who gave birth to children with a cleft palate and cleft lip. It is appropriate to note at the same time that, according to the German scientist Knerr, intensive smoking of fathers also contributes to an increase in the frequency of various developmental defects in children.

Children born from mothers who smoked during pregnancy often have altered body reactivity, weak and unstable nervous system. By one year, children of smoking mothers are catching up with the development and body weight of children of non-smoking mothers. However, there is evidence that such children lag behind their peers in growth and development by 7 years.

In addition, smoking allows you to pause between the word and the action, between the question and the answer. This is where a cigarette helps buy time to think at least a minute. Indecisive people, smoking a cigarette, seem to themselves "cooler", and teenagers - more mature. And, finally, a cigarette calms by the fact that it is in your mouth. Nature is conceived so that a person experiences a feeling of peace and comfort under the action of a sucking reflex. In the same way that a baby calms down at the mother’s breast or when he is given a pacifier, adults wake up by taking a cigarette in their mouth (the well-known remedy for insomnia is based on this: a glass warm milk drink at night through a straw).

Research scientists recent years allow us to state with all certainty that the former ideas about the benefits of smoking are nothing more than a myth. If earlier it was believed that smoking helps to cope with stress, relaxes, then new studies refute this opinion. Nicotine and other components of tobacco smoke act on receptors in the brain in such a way that they cause mood deterioration up to mental disorder. Smoking increases the likelihood of developing depression by four times.

Alcohol is a biological poison. It affects all organs and systems, disrupting their functions, significantly reduces the body's resistance to adverse effects. external environment, to the influence of toxic and infectious agents.

The drinking age has dropped dramatically in the last few years as more teenagers under the age of 13 are becoming addicted to alcohol. Adolescents reproduce the norms of female and male alcohol behavior adopted in Russian society, in which two "alcohol cultures" simultaneously coexist: "male", focused on the abuse of alcohol, and "female", focused on moderate consumption.

There are also significant differences in attitudes towards alcohol among young people from different walks of life. So. students of vocational schools (vocational schools), where adolescents from families with low social and educational status of parents are more likely to enter, drink much more often than secondary school students and are more likely to get drunk. In addition, they often “start” not with champagne or dry wine, like their more socially prosperous peers, but with the heaviest alcoholic drink - vodka.

An analysis of the motives for turning to alcohol among students of schools and vocational schools also indicates a greater degree of social deprivation of the latter. "Holidays" and "communication" - the dominant motives for alcohol consumption among schoolchildren - are less common among their peers from vocational schools than references to negative emotions and boredom (“I want to eat”, “they take money, the older guys beat me up”, “it’s cold in the hostel”, “sickening”, “uncomfortable”, “I don’t feel like anything”).

Thus, while for schoolchildren alcohol is primarily an attribute of fun, for vocational school students it is an opportunity to change mental condition, "get away" from problems they can't solve. A series of studies carried out by the sector of sociology deviant behavior Institute of Sociology of the Russian Academy of Sciences among students of several cities near Moscow, showed that the most “heavy drinkers” are working minors. once a month or more, while among them, respectively, 45.5% and 30.6% have experience of repeated severe intoxication. The reason for this is a highly alcoholic adult environment, in which working young people under the age of 20 find themselves, as a rule, in unskilled labor. It is difficult for them to avoid drinking alcohol with workmates, since in Russia, as is known, the practice of drinking at the workplace during the working day is widespread. This allows us to speak about the increasing differentiation of alcohol consumption by adolescents who grew up in different social environments.

All this inevitably leads to an increase in morbidity and mortality in people suffering from alcoholism. Drunkenness is especially acute and severe in girls and young women.

In women who drink alcohol, there are violations of menstrual and reproductive functions, sexual desire weakens. Alcohol has a detrimental effect on offspring. It is known that common cause disorders of the neuropsychic and physical development of children is the drunkenness of their parents, and sometimes even a single use of alcoholic beverages by them.

The main danger is the birth of a handicapped child with malformations. Prominent writers and scientists, such as L. N. Tolstoy, V. M. Bekhterev and others, also emphasized that nervous and mental illness, degeneration of offspring.

Drugs. Drug use, unlike alcohol use, was not until recently considered a problem traditional for Russia. It is difficult to assess which of these problems is now more relevant for young people. On the one hand, alcohol abuse in Russia is widespread, and drug use is still less widespread. The problem of use psychoactive substances The social and economic crisis has seriously changed the contingent of their adherents has become younger: the first drug trials occur as early as 13-14 years old, and sometimes even at primary school age.

Schoolchildren call the dominant motive for the first drug test "curiosity", and drug addicts who are being treated - "the desire to have fun."

Apparently, one of the main mistakes in promoting healthy lifestyles among adolescents is that the consumption of alcohol, drugs and smoking are not separated from each other, and the focus is on what harm they cause to health, while the adolescent, when making a decision about whether to try alcohol, tobacco or drugs is guided by different considerations in each case.

According to the World Health Organization, drugs ranked first among the culprits premature death people and are already ahead of cardiovascular diseases and malignant tumors. All over the world there is a wave of drug addiction among men and women. Behind them, young men, girls, teenagers and even children are drawn into this pool.

Undoubtedly, drug addiction is a serious disease and a problem for the whole society. And this disease is easier to prevent than to treat. For each person, the question sober life and life without drugs is solved differently depending on his character, interests, health, life situations.

One of the main features of the harmful effects of drugs is that it is a disease of young age, much more so than alcoholism. One of the main features of the modern incidence of drug addiction is a decrease in the lower age limit for the onset of drug addiction to 12-15 years. This is one of the dangers of addiction. "Pampering" with drugs can lead to tragedy.

Summing up all of the above, it should be noted that the sociology of health is becoming that special theory that, by its development, will further expand the scope of interests of general sociology and at the same time, at the expense of the latter, reach a higher level of theoretical development of its own issues. In its developed form, it will make it possible to overcome communication difficulties between the natural, technical and social sciences, between medicine, health care and social sciences. Its fruitful generalizations, scientific methods and particular techniques can be applied directly in the field medical research problems of health and disease, norms and pathologies.

In our time, the incompatibility of pregnancy and the use of alcoholic or narcotic stimulants has been unequivocally and convincingly proven: the risk of abortion and the birth of a sick child increases. In the early stages, the result of the action of nicotine, alcohol and drugs is the death of fertilized eggs and embryos, retarded growth and development of the fetus, impaired formation of organs and systems of the fetus, spontaneous miscarriages, stillbirths