Contents
Genetic causes of male infertility
Male factor infertility
About 4-5% of men of reproductive age suffer from infertility. In most cases, reproductive disorders are associated with impaired spermatogenesis and/or patency of the vas deferens. The influence of the “male factor” can be caused not only by the actual failure of pregnancy in a woman, but also by various forms of failed pregnancy (miscarriage). In our center you can seek advice and additional examination to identify the most common genetic factors of male infertility.
Karyotype abnormalities (chromosomal aberrations)
Chromosomal aberrations – these are changes in the number and/or structure of chromosomes. Chromosomal abnormalities in men, leading to reproductive disorders, can affect both sex chromosomes (gonosomal) and autosomes. These disorders can be regular (detected in all cells of the body) or mosaic (characterize a specific clone of cells).
Chromosomal aberrations detected only in spermatozoa are a common finding. In healthy men, 1 to 15% of sperm may have chromosomal abnormalities, most of which are structural rearrangements.
Gonosomal chromosomal abnormalities include an increase in the number of X chromosomes (Klinefelter syndrome, 47,XXY; 48,XXХY, etc.); increase in the number of Y chromosomes (47,XYY; and other poly-Y aneuploidies); translocations of Y-chromosome fragments, most often carrying the SRY gene (sex inversions 46,XX- and 45,X-males); structural abnormalities of Y chromosomes (macro- and micro-deletions, inversions, translocations, ring chromosomes, isochromosomes).
Autosomal chromosomal abnormalities include changes in the number and structure of non-sex chromosomes – inversions; translocations (Robertsonian, reciprocal); other structural abnormalities; partial deletions and duplications; trisomy (for example, Down syndrome).
Some common karyotype variants in the population (chromosomal heteromorphisms) may be a risk factor for recurrent miscarriage (inversion of chromosome 9, Inv (9); familial inversions of the Y chromosome; increased heterochromatin of the Y chromosome, Yqh+; increased/decreased pericentromeric constitutive heterochromatin; increased duplicated satellites of acrocentric chromosomes).
An increased number of chromosomal aberrations in sperm is detected in primary severe testiculopathies, as well as after radiation or chemotherapy.
In couples with recurrent miscarriage, the frequency of chromosomal abnormalities in men is about 5%. In the case of spontaneous abortions, the frequency of chromosomal abnormalities in men is 1,5-2%; if spontaneous abortions are combined with stillbirths or congenital malformations, the frequency of karyotype abnormalities in men is 4-4,5%.
Male factor gene mutations
Normal development and maintenance of reproductive function in men is controlled by about 2000 genes. Mutations in these genes can lead to diseases in which decreased fertility may be the main symptom or part of a broader symptom complex. The main groups of reproductive disorders that develop as a result of gene mutations:
Disorders of differentiation and development of reproductive system organs:
- Pseudohermaphroditism
- Gender inversion
- Denis-Dresch syndrome
- Pseudovaginal hypospadias
- Cryptorchidism
- Bilateral absence of vas deferens syndrome
- Persistent Müllerian duct syndrome
Endocrine disorders:
- Hypogonadotropic hypogonadism
- Decreased sensitivity to gonadotropin
- Disorders of steroid hormone biosynthesis
- Disorders of steroid hormone metabolism
- Disorders of the action of steroid hormones
Impaired formation and functioning of sperm:
- Myotonic dystrophy
- Noonan syndrome
- sickle cell anemia
- Thalassemia
- Kartagener’s syndrome
- Primary ciliary dyskinesia
- Fanconi anemia
- Ataxia-telangiectasia