Evaluation of Genetic Risk Factors in Male Reproductive Pathology: Latvian Population Study. Summary of the Doctoral Thesis

Abstract

Infertility is a topical problem nowadays. This problem affects approximately 10-15% of couples and about half of the cases refer to male infertility. Genetic reasons for male infertility should be looked in genes that are involved in normal male development and spermatogenesis processes. Those genes are located on human Y chromosome and on autosomes. Fertility markers-genes localised on human Y-chromosome enable scientists to study Y-chromosomal AZF (azoospermia) region microdeletions and their correlation with male infertility. The method of molecular genetic analysis of spermatogenesis disturbances has been introduced; and it has been found that frequency of Y chromosome microdeletions among infertile males is 5%, and AZF microdeletions were observed in cases of azoospermia or severe oligozoospermia. An algorithm has been developed, which can help select those infertility cases, when detection of Y chromosome microdeletions is purposeful. Polymorphisms, characteristic to human Y chromosome, - biallelic markers and microsatellites – can be successfully applied for detection of existence of “infertility haplogroups”. Studying incidence of Y haplogroups in the infertile males and control group, statistically significant differences have been found, which suggests possibility of existence of certain Y chromosome variants – “infertility” haplogroups. Positive correlation exists between male infertility and mutations or polymorphisms found in CFTR gene (localised on human chromosome 7). Analyzing CFTR gene mutations delF508, R117H, as well as 8th intron poly-T and poly-TG polymorphisms in males with idiopathic infertility and control group, statistically significant relation of these mutations and polymorphisms with male infertility was not found, which indicates that CFTR gene does not affect spermatogenesis process directly. Gathering information about the cause of genetic risk of male infertility, the study deals with molecular genetic aspect that has not been studied in Latvia up to now, and is significant in genetic counselling of these patients.