Symptoms of the disease are reproductive dysfunction. Levels of sex differentiation and their disorders

Comprehensive research, which allows you to determine the leading genetic causes of male infertility and choose the appropriate tactics for patient management.

The study included the most common genetic causes of male infertility: identification of deletions in the locus AZF affecting spermatogenesis, determining the number of CAG repeats in the gene AR associated with changes in sensitivity to androgens and search for mutations in the gene CFTR, responsible for the development of the disease, the clinical manifestation of which is obstructive azoospermia.

What biomaterial can be used for research?

Buccal (buccal) epithelium, venous blood.

How to properly prepare for research?

No preparation required.

General information about the study

Male infertility (MF) is serious pathological condition, requiring complex comprehensive diagnosis, urgent correction, and in some cases prevention.

15-20% of couples suffer from infertility reproductive age. In half of the cases it is associated with the “male factor”, manifested by deviations in the parameters of the ejaculate.

The difficulty of diagnosing MB lies in large quantities the reasons that cause it. These include anomalies genitourinary system, tumors, genitourinary tract infections, endocrine disorders, immunological factors, genetic mutations etc. Unlike the above reasons, genetic ones do not always have clinical manifestations, however, they are extremely important for diagnosing MB in the subject.

It is important to understand that the diagnosis of “MB” and its forms can be made only specialist doctor based on anamnestic data, examination data, instrumental and laboratory research. The reasons for visiting a doctor may be the following:

• inability to conceive a child within a year if there are no signs female infertility at the partner's;
• erectile and ejaculatory dysfunction;
• concomitant diseases of the urogenital area (inflammatory, tumor, autoimmune, congenital, etc.);
• taking hormonal and cytostatic drugs;
• discomfort in the urogenital area.

Frequent causes of male infertility are disturbances in the structure and quantity of sperm, affecting their motility and ability to fertilize.

The main genetic reasons for the development of MB are:

1) deletions (removal of genetic fragments) of the locus AZF;

2) polymorphism (increase in repeats of a genetic fragment - CAG) of the gene AR;

3)m mutations (sequence violation) of a gene CFTR .

Currently, these markers are an integral part of standard criteria for complex diagnostics genetic manifestations MB, occurring in a group of patients in 10-15% of cases.

Deletions of the AZF locus and the SRY gene

Important role in the development of pathologies such as oligozoospermia and azoospermia, deviations in a specific region of the Y chromosome play a role - AZF- locus (azoospermia factor). Included in him determine the normal course of spermatogenesis, and in case of violation of the genetic structure AZF-locus, the formation of male germ cells can be seriously disrupted.

AZF- locus is in long shoulder Y chromosomes (q11). The genes located in this locus play an important role in the process of spermatogenesis.

Microdeletion of the Y chromosome is the loss of certain areas, found on average in 10-15% of cases of azoospermia and in 5-10% of cases of severe oligozoospermia and causes spermatogenesis disorders and infertility in men.

AZF locus divided into 3 sections: AZFa, AZFb And AZF c. In each of them, genes involved in the control of spermatogenesis have been identified. Deletions in the AZF locus may be full, i.e. completely removing one of AZF-regions or more, and partial, when they do not completely capture any of its three regions.

When full AZF-deletions, there is a fairly clear dependence of the degree of impairment of spermatogenesis on the size and location of the deletions, which may have prognostic value in obtaining sperm suitable for programs in vitro fertilization.

• Absence of the entire locus AZF, as well as deletions that completely cover regions AZFa and/or AZFb, indicate the impossibility of obtaining sperm.
• Almost all patients with deletions AZFb or AZFb+c Azoospermia is noted due to severe disorders of spermatogenesis (Sertoli cell only syndrome).
• With complete deletions of the region AZFc manifestations range from azoospermia to oligozoospermia. On average, 50-70% of patients with a deletion involving the entire AZF c-region, it is possible to obtain sperm suitable for artificial insemination.
• With partial AZF In c-deletions, manifestations range from azoospermia to normozoospermia.

State Research AZF- Y-chromosome locus in patients with severe azoospermia and oligozoospermia makes it possible to establish the genetic cause of spermatogenesis disorders and carry out differential diagnosis infertility in men and adjust treatment, check the possibility of obtaining sperm from testicular biopsy and the possibility of obtaining sperm for ICSI (intracytoplasmic sperm injection).

It should be taken into account that in case successful use assisted reproductive technologies, deletion of the Y chromosome is transmitted through the male line. This shows the need dispensary observation for boys born after the use of ICSI to fathers with microdeletions in the Y chromosome, to assess their fertility status.

Indications for screening AZF-deletions are based on sperm count and include azoospermia and severe oligozoospermia (

In the genetic control of development by male type gene is especially important SRY(Sex-determining Region Y). It is in it that the largest number of mutations associated with gonadal dysgenesis and/or sex inversion were found. If there is no part of the chromosome containing the gene SRY, the phenotype will be female with a male karyotype of 46XY.

At this time genetic research includes analysis AZF-chromosomal locus – 13 clinically significant deletions: sY86, sY84, sY615, sY127, sY134, sY142, sY1197, sY254, sY255, sY1291, sY1125, sY1206, sY242, as well as determination of gene deletion SRY.

Androgen receptor gene AR

Another determining factor in male infertility is a violation of the hormonal regulation of spermatogenesis, in which the male sex hormones androgens play a key role. They interact with specific androgen receptors, determining the development of male sexual characteristics and activating spermatogenesis. Receptors are found in the cells of the testes, prostate, skin, cells nervous system and other fabrics. The androgen receptor gene is characterized by the presence of a CAG (cytosine-adenine-guanine) repeat sequence, the number of which can vary significantly (from 8 to 25). The CAG triplet encodes the amino acid glutamine, and when the number of CAG nucleotide repeats changes, the amount of the amino acid glutamine in the protein changes accordingly. From the number of repeats in the gene AR the sensitivity of the receptor to , and the relationship is inversely proportional: the more repetitions, the less sensitive the receptor. An increase in the number of CAG repeats in receptors reduces their activity, they become less sensitive to testosterone, which can lead to impaired spermatogenesis, and the risk of developing oligozoospermia and azoospermia increases. There is also evidence that with a reduced number of CAG repeats (AR) increased sensitivity to androgens and increases the risk in men. An increase in the number of CAG repeats to 38-62 leads to spinobulbar muscular atrophy, Kennedy type.

The test result makes it possible to assess the activity of spermatogenesis and, if necessary, take appropriate measures to compensate for the pathology.

Male infertility in cystic fibrosis

Luteinizing hormone (LH)

Follicle stimulating hormone (FSH)

Prostate-specific antigen total (PSA total)

Karyotype study

Important Notes

Lifetime data genetic markers do not change, the study is carried out once.

Literature

1. Naina Kumar and Amit Kant Singh Trends in male factor infertility, an important cause of infertility: A review of literature J Hum Reprod Sci. 2015 Oct-Dec; 8(4): 191–196.

What could be a more pleasant event than happy marriage? After thinking logically, most come to the answer. The best thing is the opportunity to become happy parents. Most often, every married couple sooner or later thinks about this important step like giving birth to a child. However, unfortunately, not everyone succeeds in implementing their plans on the first try, and for 15% of couples such efforts are doomed to failure. What could cause this situation?

When faced with a similar problem, do not panic. If the desire to have a child does not come true within 2-7 months, it’s not a big deal. You need to calm down and not focus on it. There are many reasons why pregnancy does not occur: from simple psychological factor before serious problems develop.

TO similar problems include:

male infertility;

female infertility;

immunological incompatibility (a woman is allergic to components male sperm) – in this case, neither spouse suffers from pathologies that can cause infertility, but such a couple cannot have children together;

psychological aspects.

However, if you completely healthy woman If you have regular sexual intercourse without using contraception for a year, pregnancy does not occur, then it’s time to think that the problem may be with the man. It’s worth talking about this situation in more detail - what is it? How to diagnose? How to treat?

Male infertility - despite regular sexual intercourse - is the inability of a man's sperm to fertilize a woman's egg. Ideally, in the spermogram of a healthy man, 1 ml of sperm should contain about 20 million sperm, which are rapidly moving forward and are capable of fertilization. Also, about 50% of sperm should have the correct structure.

Causes

Reasons that can cause infertility in men may include:

complication after mumps;

inflammation of the genitourinary organs;

diabetes mellitus (ejaculation disorders);

a small number and sluggish activity of sperm in the semen (the complete absence of “tadpoles” is also possible);

psychological infertility (when a man is subconsciously susceptible to fear of future responsibility that will arise with the birth of a baby or in the presence of other obsessive fears and arguments);

immunological infertility (the formation of antibodies that prevent sperm from performing their normal functions).

Well, the simplest and most common reason that comes to mind last is the presence bad habits. Smoking and alcohol abuse also have a detrimental effect on a man’s body in general and on reproductive function in particular.

Diagnostics

Male infertility is divided into:

primary – in which a man was unable to fertilize any representative of the opposite sex;

secondary - when at least one woman became pregnant from a particular man.

Reveal this pathology in a man, a urologist-andrologist and an endocrinologist-andrologist will help determine the cause of this condition. The beginning of the research is to undergo a semen analysis. Such an analysis is usually called a spermogram. It determines the activity and viability of sperm, in addition, other pathological changes are assessed.

Doctors may also recommend other tests to determine exact reason or pathologies:

Ultrasound of the prostate gland;

hormone analysis;

diagnosing immune infertility– MAR test;

bacteriological culture for detection infectious pathologies genitourinary area.

Depending on the test results, the specialist will prescribe treatment. Therapy is divided into three methods, which will be discussed below.

Treatment methods

Conservative therapy

Consists of using medications in the presence of sexually transmitted infections of various origins. This type of treatment is also often prescribed in the presence of infertility due to hormonal imbalance.

Surgery

Prescribed in the presence of anomalies urethra, in the presence of inguinal hernias and other anatomical abnormalities that cannot be corrected without surgery.

Alternative therapy

This method is used when there is serious violations reproductive function in the stronger sex. It involves the artificial introduction of sperm into the woman's genital tract to achieve fertilization.

Treatment of infertility must be comprehensive and adequate. In addition, the stronger sex (not only when making a diagnosis, but also when planning pregnancy) must reconsider their own rhythm of life and regulate it if necessary. It’s worth giving up bad habits, starting to eat right and not forgetting about good rest. Problem solving of an intimate nature in men can be achieved through the use of herbal medicines for the treatment and prevention of pathologies of the male reproductive system. Quite often, after normalizing your own diet and rest regime and following simple rules, reproductive function is normalized without additional interventions.

IN Lately in reproductive medicine the influence of biological factors is being actively studied male body on his fertility (fertility), as well as on the health of the offspring. Let's try to answer some questions related to this topic. The ability to reproduce, or reproduce, is the main distinguishing feature of living beings. In humans, for the successful implementation of this process, the preservation of reproductive function is required - both on the part of the woman and on the part of the man. Totality various factors, influencing the reproductive ability (fertility) in men is called the “male” factor. Although in most cases this term refers to various circumstances that adversely affect male fertility, of course, the “male” factor should be considered as a broader concept.

Infertility in marriage, ineffectiveness of its treatment, including with the help of assisted reproduction methods (in vitro fertilization, etc.), various shapes miscarriage (recurrent miscarriage), such as frozen pregnancy, spontaneous miscarriages, may be associated with negative impact"male" factor. If we consider the genetic contribution of parents to the health of their offspring, in general it is approximately the same for both women and men. It has been established that the cause of infertility in marriage in about a third of cases is a violation of reproductive function in a woman, in a third - in a man, and in a third of cases there is a combination of such disorders in both spouses.

Causes of male infertility

Infertility in men is most often associated with impaired patency of the vas deferens and/or sperm formation (spermatogenesis). Thus, in approximately half of cases of infertility in men, a decrease in the quantitative and/or qualitative parameters of sperm is detected. There is great amount causes of reproductive dysfunction in men, as well as factors that may predispose to their occurrence. These factors can be physical in nature (exposure to high or low temperatures, radioactive and other types of radiation, etc.), chemical (exposure to various toxic substances" by-effect medications, etc.), biological (sexually transmitted infections, various diseases internal organs) and social (chronic stress). The cause of infertility in men may be associated with the presence of hereditary diseases, diseases of the endocrine system, autoimmune disorders - the production of antibodies in a man’s body to his own cells, for example to sperm.

The cause of reproductive problems in men can be genetic disorders, in particular changes in genes that are involved in the control of any processes occurring in the body.

To a large extent, the state of reproductive function in men depends on development of the genitourinary system, puberty. Processes that control development reproductive system, begin to work in intrauterine period. Even before the formation of the gonads, primary germ cells are released outside the tissues of the embryo, which move to the area of ​​​​the future testicles. This stage is very important for future fertility, since the absence or insufficiency of primary germ cells in the developing testes can cause serious disorders of spermatogenesis, such as the absence of sperm in the seminal fluid (azoospermia) or severe oligozoospermia (sperm count less than 5 million / ml ). Various violations The development of the gonads and other organs of the reproductive system is often due to genetic reasons and can lead to impaired sexual development and, in the future, to infertility or decreased fertility. Hormones, primarily sex hormones, play an important role in the development and maturation of the reproductive system. Various endocrine disorders associated with deficiency or excess of hormones, impaired sensitivity to any hormone that controls the development of the organs of the reproductive system, often lead to insufficient reproductive function.

The central place in the male reproductive sphere is occupied by spermatogenesis. This is a complex multi-stage process of development and maturation of sperm from immature germ cells. On average, sperm maturation takes about two and a half months. The normal course of spermatogenesis requires the coordinated influence of numerous factors (genetic, cellular, hormonal and others). This complexity makes spermatogenesis an “easy target” for all kinds of negative impacts. Various diseases, unfavorable environmental factors, unhealthy lifestyle (low physical activity, bad habits, etc.), chronic stressful situations, including those related to labor activity, can lead to impaired spermatogenesis, and, as a result, to decreased fertility.

Over the past decades, there has been a clear deterioration in sperm quality. In this regard, standards for the quality of seminal fluid have been repeatedly revised. Plank normal amount(concentration) of sperm has been reduced several times and is now 20 million/ml. It is believed that the reason for this “decline” in sperm quality is primarily related to the deterioration of the environmental situation. Of course, with age there is a decrease in the quantity and quality of sperm (number, motility and proportion of normal sperm), as well as other sperm parameters that can affect male fertility. However, it should be noted that the state of spermatogenesis is largely determined by genetic factors, the presence of diseases and/or factors that adversely affect the formation of sperm.

Despite the use of numerous modern diagnostic methods, the cause of infertility remains unclear in almost half of all cases. The results of numerous studies indicate that genetic causes occupy one of the leading places among the causes of both infertility and recurrent miscarriage. In addition, genetic factors may be the root cause of abnormalities of sexual development, as well as a number of endocrinological, immunological and other diseases leading to infertility.

Chromosomal mutations (change in the number and/or structure of chromosomes), as well as disorders of genes that control reproductive function in men can cause infertility or miscarriage. Thus, very often male infertility, associated with a severe disorder of spermatogenesis, is caused by numerical abnormalities of the sex chromosomes. Abnormalities of the Y chromosome in a certain region are one of the most common genetic causes (about 10%) of infertility in men associated with azoospermia and severe oligozoospermia. The frequency of these disorders reaches 1 in 1000 men. Impaired patency of the vas deferens may be due to the presence of such a common genetic disease as cystic fibrosis (cystic fibrosis of the pancreas) or its atypical forms.

In recent years, the influence of epigenetic (supragenetic) factors on reproductive function and their role in hereditary pathology. Various supramolecular changes in DNA, not associated with a violation of its sequence, can significantly determine the activity of genes and even be the cause of a number of hereditary diseases(so-called imprinting diseases). Some researchers point to a several-fold increase in the risk of such genetic diseases after using in vitro fertilization methods. Undoubtedly, epigenetic disorders can cause reproductive dysfunction, but their role in this area remains poorly understood.

It is important to note that genetic causes do not always result in primary infertility (when pregnancy has never occurred). In some cases of secondary infertility, i.e. when recurrent pregnancies do not occur, the cause may be due to genetic factors. Cases have been described in which men who have already had children subsequently experienced severe disturbances in spermatogenesis and, as a consequence, infertility. Therefore, genetic testing for patients or couples with reproductive problems carried out regardless of whether they have children or not.

Ways to overcome infertility

Overcoming infertility, including in some cases such severe forms of reproductive disorders in men as azoospermia (lack of sperm in the ejaculate), oligozoospermia (decrease in the number of sperm) and asthenozoospermia (decrease in the number of motile forms, as well as the speed of sperm movement in the semen) severe, became possible thanks to the development of in vitro fertilization (IVF) methods. More than ten years ago, an IVF method was developed, such as fertilization of an egg with a single sperm (ICSI, Intracytoplasmic Sperm Injection). Like conventional in vitro fertilization, this technique is widely used in IVF clinics. However, it should be remembered that the use of assisted reproductive technologies can not only solve the problem of childbearing, but also transmit genetic disorders, increasing the risk of inheriting mutations associated with reproductive pathology. Therefore, all patients, as well as germ cell donors, must undergo a medical genetic examination and counseling before IVF programs.

A cytogenetic study (analysis of a set of chromosomes) is prescribed to all married couples with infertility or recurrent miscarriage. If indicated, additional genetic studies are recommended.

Unlike women (especially those over 35 years old), men with age do not experience a significant increase in the number of germ cells with an incorrect set of chromosomes. Therefore, it is believed that a man’s age does not affect the frequency chromosomal abnormalities in the offspring. This fact is explained by the peculiarities of female and male gametogenesis - the maturation of germ cells. In women, at birth, the ovaries contain a final number of germ cells (about 450-500), which are used only with the onset of puberty. Division of germ cells and maturation of sperm persists in men until old age. Most chromosomal mutations occur in germ cells. On average, 20% of all oocytes (eggs) of healthy young women carry chromosome abnormalities. In men, 5 - 10% of all sperm have chromosomal disorders. Their frequency may be higher if there are changes (numerical or structural chromosome abnormalities) in the man’s chromosome set. Severe disturbances in spermatogenesis can also lead to an increase in the number of sperm with an abnormal set of chromosomes. It is possible to assess the level of chromosomal mutations in male germ cells using a molecular cytogenetic study (FISH analysis) of sperm. Such a study on embryos obtained after in vitro fertilization makes it possible to select embryos without chromosomal abnormalities, as well as to select the sex of the unborn child, for example, in the case of hereditary diseases linked to sex.

Regardless of age, married couples planning a pregnancy and concerned about the health of their future offspring, in particular the birth of children with genetic disorders, can seek appropriate help from medical genetic consultations. Carrying out a genetic examination allows us to identify the presence of factors that are not conducive to the birth of healthy offspring.

If there is no reason to worry about this, any special training To future pregnancy is not carried out. And if necessary, given the duration of sperm maturation, such preparation should begin at least three months in advance, and preferably six months to a year. During this period, it is advisable not to use strong medications. A man should abstain or get rid of bad habits, and, if possible, eliminate or reduce the influence of professional and other harmful factors. A reasonable balance between physical activity and rest is very useful. It is important to remember that the psycho-emotional mood is of no small importance for a married couple planning a pregnancy.

Undoubtedly, the biological components transmitted to the child from the parents are quite important. However, social factors also have a significant impact on the health and development of the child. Numerous studies have shown that the level intellectual abilities and a person’s character are to a certain extent determined by genetic factors. However, it should be noted that the degree of development mental abilities is largely determined by social factors - upbringing. The age of parents in itself cannot influence the level of development of children. Therefore, the widespread belief that older fathers are more likely to give birth to geniuses is unfounded.

To summarize, I would like to note that the health of a child equally depends on the health of both parents. And it’s good if the future dad and future mom will keep this in mind.

Most known mutations lead to the absence or delay of puberty and, as a consequence, to infertility. However, people who consult a doctor about infertility have sexual development fine. Testing for most mutations leading to infertility is currently of no practical use. However, some cases deserve special mention because they occur frequently in everyday practice.

Bilateral aplasia of the vas deferens

Bilateral aplasia of the vas deferens occurs in 1-2% infertile men. According to most data, in 75% of cases, mutations of the CF gene are detected, leading to cystic fibrosis. The main risk in such cases is the possibility of giving birth to a child with cystic fibrosis. It is necessary to examine both partners for the presence of mutations, and then provide appropriate counseling. If both partners are carriers of cystic fibrosis, the risk in the child reaches 25% (depending on the nature of the mutation). Even if only one mutation leading to cystic fibrosis is found in a man, and the woman is not a carrier, it is better to play it safe and refer the couple for consultation with a geneticist. In approximately 20% of cases, bilateral aplasia of the vas deferens is accompanied by renal malformations, and in one study, no mutations leading to cystic fibrosis were identified in such patients (although the number of mutations analyzed was small).

It should be emphasized that the purpose of mass screening is to identify cystic fibrosis, not aplasia. The combinations of mutations leading to aplasia of the vas deferens are varied and complex, making counseling for this disease difficult. In the first studies on the genetics of bilateral aplasia of the vas deferens, there was not a single participant homozygous for the AF508 mutation, the most common mutation in the CF gene, which occurs in 60-70% of cases in the classical form of cystic fibrosis. In approximately 20% of patients, two mutations in the CF gene, characteristic of cystic fibrosis, are found at once - in many cases these are missense mutations (a combination of two alleles that cause light form cystic fibrosis, or one allele causing a mild form of the disease and one causing a severe form). A polymorphism was also discovered in intron 8, in which the number of thymines in different alleles is 5, 7 or 9. In the presence of the 5T allele, exon 9 is skipped during transcription, and the mRNA, and subsequently the protein, are shortened. The most common genotype for bilateral aplasia of the vas deferens (about 30% of cases) is a combination of the allele carrying the mutation causing cystic fibrosis and the 5T allele.

The R117H mutation is included in mass screening because its combination with other, more severe mutations in the CF gene can cause cystic fibrosis. When the R117H mutation is detected, a derivative test is performed for the presence of the 5T/7T/9T polymorphism. When a 5T allele is detected, it is necessary to determine whether it is on the same chromosome as R117H (i.e., in a cis position) or on the other (in a trans position). The 5T allele in the c-position relative to R117H causes cystic fibrosis, and if a woman is also a carrier of one of the alleles, causing disease, the risk of cystic fibrosis in a child is 25%. The complexity of the genetics of cystic fibrosis becomes apparent when looking at the diversity of phenotypes in homozygotes for the 5T allele. The presence of the 5T allele reduces the stability of mRNA, and it is known that patients whose level of unchanged mRNA is 1-3% of normal develop cystic fibrosis in the classical form. When the level of unchanged mRNA is more than 8-12% of the norm, the disease does not manifest itself, and at intermediate levels different options are possible, from complete absence manifestations of the disease to bilateral aplasia of the vas deferens and light form cystic fibrosis. It should also be noted that aplasia of the vas deferens in mild cases can also be unilateral. In the general population, the 5T allele occurs with a frequency of about 5%, with unilateral aplasia of the vas deferens - with a frequency of 25%, and with bilateral aplasia - with a frequency of 40%.

American College medical geneticists and the American College of Obstetricians and Gynecologists recommend identifying only 25 mutations whose prevalence in the US population is at least 0.1%, and testing for the 5T/7T/9T polymorphism only as a derivative test. However, in practice, many laboratories can reduce costs by including this analysis in the main program, which, as shown above, can lead to enormous difficulties in interpreting the results. It should be remembered that the purpose of mass screening is to identify cystic fibrosis.

Genes regulating spermatogenesis

Genes presumably responsible for spermatogenesis are mapped on the Y chromosome in the AZF region, located in the Yq11 locus (the SR Y gene is located on the short arm of the Y chromosome). In the direction from the centromere to the distal part of the arm, sections AZFa, AZFb and AZFc are located sequentially. The AZFa region contains the USP9Y and DBY genes, the AZFb region contains the RBMY gene complex, and the /4Z/c region contains the DAZ gene.

Some genes involved in the regulation of spermatogenesis are represented in the genome by several copies. There appear to be 4-6 copies of the DAZ gene and 20-50 genes or pseudogenes of the RBMY family in the genome. DBY and USP9Y are represented in the genome by a single copy. Because of large number Due to repetitive sequences and differences in study design, analysis of the regions of the Y chromosome that control spermatogenesis is fraught with considerable difficulties. For example, detection of deletions in the AZF region has been carried out largely by analyzing DNA marking sites, short DNA sequences with a known chromosomal location. The more of them analyzed, the higher the likelihood of detecting deletions. In general, deletions in the AZF region are more common in infertile men, but they have also been found in healthy men.

Evidence that the AZF region contains genes regulating spermatogenesis was provided by an intragenic deletion in the USP9Y gene, which is also called DFFRY (since it is homologous to the corresponding faf gene in Drosophila). The infertile man had a four base pair deletion that his healthy brother did not have. These observations, coupled with in vitro data, suggested that a mutation in the USP9Y gene impairs spermatogenesis. In a reanalysis of previously published data, the researchers identified another single deletion in the USP9Y gene that impairs spermatogenesis.

A review of nearly 5,000 infertile men testing for mutations on the Y chromosome found that about 8.2% of cases (compared with 0.4% of healthy men) had deletions in one or more parts of the AZF region. In individual studies, rates ranged from 1 to 35%. According to the mentioned review, deletions are most often found in the AZFc region (60%), followed by AZFb (16%) and AZFa (5%). The remaining cases are a combination of deletions in several regions (most often including deletions in AZFc). Most mutations were found in men with azoospermia (84%) or severe oligozoospermia (14%), defined as a sperm count of less than 5 million/ml. Interpretation of data on deletions in the AZF region is extremely difficult because:

1. they are found both in infertile people and in healthy men;
2. the presence of DAZ and RBMY clusters containing several copies of genes makes analysis difficult;
3. V various studies various sperm parameters were studied;
4. the set of contig maps of the Y chromosome was not complete due to the presence of repeated sequences;
5. there was insufficient data from healthy men.

In a double-blind study, sex hormone levels, semen parameters and AZF region analysis were determined in 138 male IVF couples, 100 healthy males and 107 young Danish military personnel. To study the AZF region, 21 DNA tagging sites were used; with normal sperm parameters and in all cases where the sperm count exceeded 1 million/ml, no deletions were found. In 17% of cases of idiopathic azoospermia or cryptozoospermia and in 7% of cases with other types of azoospermia and cryptozoospermia, deletions in the AZFc region were detected. It is interesting to note that none of the study participants had deletions in the AZFa and AZFb regions. This suggests that genes located in the AZFc region are most important for spermatogenesis. Later more than major study, which gave similar results.

If deletions are detected on the Y chromosome, this should be discussed with both future parents. The main risk for offspring is that sons may inherit this deletion from their father and will be infertile - such cases have been described. These deletions do not appear to affect the effectiveness of IVF or pregnancy rates.

Fragile X syndrome in women with premature ovarian failure

In sporadic cases of premature ovarian failure, approximately 2-3% of women are found to have a premutation in the FMR1 gene, which is responsible for the occurrence of fragile X syndrome; in women with hereditary premature failure In ovaries, the frequency of this premutation reaches 12-15%. The fragile region at the Xq28 locus can be identified by karyotyping cells grown in folate-deficient conditions, but DNA analysis is usually performed. Fragile X syndrome refers to diseases that are caused by an increase in the number of trinucleotide repeats: normally the FMR1 gene contains less than 50 repeats of the CCG sequence, in premutation carriers their number is 50-200, and in men with fragile X syndrome - more than 200 ( complete mutation). Fragile X syndrome is characterized by an X-linked dominant mode of inheritance with incomplete penetrance.

It is important to identify carriers of the premutation, since they may also be other family members: they may have sons with fragile X syndrome, which manifests itself as mental retardation, characteristic features face and macroorchidism.

Secondary hypogonadism and Kallmann syndrome in men

Men with Kallmann syndrome are characterized by anosmia and secondary hypogonadism; facial defects in the midline, unilateral renal agenesis and neurological disorders- synkinesis, oculomotor and cerebellar disorders. Kalman syndrome is characterized by an X-linked recessive pattern of inheritance and is caused by mutations in the KALI gene; suggest that Kallmann syndrome is responsible for 10-15% of cases of isolated deficiency of gonadotropic hormones in men with anosmia. Recently, an autosomal dominant form of Kallmann syndrome was discovered, which is caused by mutations in the FGFR1 gene. In isolated deficiency of gonadotropic hormones without anosmia, mutations are most often found in the GnRHR gene (gonadotropin-releasing hormone receptor gene). However, they account for only 5-10% of all cases.

Violations and their causes in alphabetical order:

reproductive dysfunction -

Reproductive dysfunction(infertility) - inability married couple to conception with regular unprotected sexual intercourse for 1 year (WHO).

In 75-80% of cases, pregnancy occurs during the first 3 months of regular sexual activity of young, healthy spouses, that is, when the husband is under 30 and the wife is under 20 years old. In the older age group (30-35 years), this period increases to 1 year, and after 35 years - more than 1 year.

Approximately 35-40% infertile couples its cause is a man, in 50% it is a woman, and in 15-20% there is a mixed factor of reproductive dysfunction.

What diseases cause reproductive dysfunction?

Causes of reproductive dysfunction in men

I. Parenchymal (secretory) disorder of reproductive function - a disorder of spermatogenesis (sperm production in the convoluted seminiferous tubules of the testicles), which manifests itself in the form of aspermia (the absence of spermatogenesis cells and spermatozoa in the ejaculate), azoospermia (the absence of spermatozoa in the ejaculate when spermatogenesis cells are detected), sperm , decreased motility, abnormal sperm structure:

1. Testicular dysfunction:
- cryptorchidism, monorchidism and testicular hypoplasia
- orchitis (viral etiology)
- testicular torsion
- primary and secondary congenital hypogonadism
- elevated temperature- violation of thermoregulation in the scrotum (varicocele, hydrocele, tight clothing)
- Sertoli cell-only syndrome
- diabetes
- excessive physical stress, psychological stress, severe chronic diseases, vibration, body overheating (work in hot shops, sauna abuse, fever), hypoxia, physical inactivity
- endogenous and exogenous toxic substances (nicotine, alcohol, drugs, chemotherapy, occupational hazards)
- radiation therapy
- mutations: mutation of the mucoviscidosis gene ( congenital absence vas deferens - obstructive azoospermia, determined by the polymerase method chain reaction; microdeletion of the Y chromosome (impaired spermatogenesis various degrees severity of karyotype disturbance - structural chromosomal aberrations - Klinefelter syndrome, XYY syndrome, chromosomal translocations, autosomal aneuploidies) - fluorescent hybridization method (FISH) using fluorochrome-labeled probes to various chromosomes

2. Hormonal (endocrine) disorder of reproductive function - hypogonadotropic hypogonadism- deficiency of luteinizing (LH) and follicle-stimulating (FSH) hormones of the pituitary gland, which play a role in the formation of testosterone and sperm:
- Pathology of the hypothalamus region
o Isolated gonadotropin deficiency (Kalman syndrome)
o Isolated luteinizing hormone deficiency (“fertile eunuch”)
o Isolated FSH deficiency
o Congenital hypogonadotropic syndrome
- Pathology of the pituitary gland
o Pituitary insufficiency (tumors, infiltrative processes, operations, radiation)
o Hyperprolactinemia
o Hemochromatosis
o The influence of exogenous hormones (excess estrogens and androgens, excess glucocorticoids, hyper- and hypothyroidism)

3. autoimmune processes - destruction of sperm by one’s own immune cells, production of antibodies to sperm
o parotitis- "pig"
o testicular injuries
o cryptorchidism (undescended testicles)
o operations on the scrotal organs
o passive homosexuals

II. Obstructive (excretory) reproductive dysfunction is associated, as a rule, with bilateral, temporary or permanent violation patency (obstruction, obstruction) of the vas deferens and impaired exit constituent elements sperm (sperm, prostate secretion, seminal vesicle secretion) through the genital tract into the urethra:
- congenital underdevelopment or absence of the vas deferens, disruption of its patency, lack of connection between the epididymal tubule of the vas deferens and the ejaculatory duct
- müllerian duct cysts of the prostate gland
- inflammatory process in the genital organs, complicated by obliteration of the vas deferens - chronic epididymitis, deferentitis, spermatocele
retrograde ejaculation - aspermatism (lack of ejaculate during sexual intercourse) with congenital or cicatricial changes in the urethra at the level spermatic tubercle, stricture of the membranous part of the urethra, damage to the nerve centers that regulate ejaculation.
- injuries to the genital organs, including during surgical interventions(for example, during hernia repair),
- consequences of vasoresection

III. Mixed reproductive dysfunction (excretory-toxic, or excretory-inflammatory) is the result of indirect toxic damage to the spermatogenic epithelium, disruption of the synthesis and metabolism of sex hormones and the direct damaging effect of pus and bacterial toxins on sperm. Biochemical characteristics of sperm:
- sperm vulnerability to immune system due to impaired maturation, enveloping with protection from proteins in the ovarian appendages (epididymitis)
- changes in the composition of prostate secretions, seminal vesicles (prostatitis, vesiculitis), STIs
- other inflammatory diseases of the male reproductive system (urethritis)

IV. Other causes of reproductive dysfunction
- problems of a sexual nature - erectile disfunction, ejaculation disorders
- anejaculation, aspermia - psychological, neurological (damage spinal cord)

V. Idiopathic disorder of reproductive function
The cause cannot be determined.

Causes of reproductive dysfunction in women
- inflammatory processes and their consequences ( adhesive process in the pelvis and obstruction fallopian tubes- “tubal-peritoneal factor)
- endometriosis
- hormonal disorders
- uterine tumors (fibroids)
- ovarian tumors (cystoma)

Which doctors should you contact if reproductive dysfunction occurs:

Have you noticed reproductive dysfunction? Do you want to know more detailed information or do you need an inspection? You can make an appointment with a doctor– clinic Eurolab always at your service! The best doctors will examine you and study you external signs and will help you identify the disease by symptoms, advise you and provide necessary help. you also can call a doctor at home. Clinic Eurolab open for you around the clock.

How to contact the clinic:
Phone number of our clinic in Kyiv: (+38 044) 206-20-00 (multi-channel). The clinic secretary will select a convenient day and time for you to visit the doctor. Our coordinates and directions are indicated. Look in more detail about all the clinic’s services on it.

(+38 044) 206-20-00

If you have previously performed any research, Be sure to take their results to a doctor for consultation. If the studies have not been performed, we will do everything necessary in our clinic or with our colleagues in other clinics.

Do you have reproductive function problems? It is necessary to take a very careful approach to your overall health. People don't pay enough attention symptoms of diseases and do not realize that these diseases can be life-threatening. There are many diseases that at first do not manifest themselves in our body, but in the end it turns out that, unfortunately, it is too late to treat them. Each disease has its own specific signs, characteristic external manifestations - the so-called symptoms of the disease. Identifying symptoms is the first step in diagnosing diseases in general. To do this, you just need to do it several times a year. be examined by a doctor to not only prevent terrible disease, but also to maintain a healthy spirit in the body and the organism as a whole.

If you want to ask a doctor a question, use the online consultation section, perhaps you will find answers to your questions there and read self care tips. If you are interested in reviews about clinics and doctors, try to find the information you need on. Also register on medical portal Eurolab to keep abreast of the latest news and information updates on the site, which will be automatically sent to you by email.

The symptom chart is for educational purposes only. Do not self-medicate; For all questions regarding the definition of the disease and methods of its treatment, consult your doctor. EUROLAB is not responsible for the consequences caused by the use of information posted on the portal.

If you are interested in any other symptoms of diseases and types of disorders, or you have any other questions or suggestions, write to us, we will definitely try to help you.