Genetika moške neplodnosti (Slovene)

Male infertility may be due to environmental or genetic factors, most often due to the complex interaction between both of them. Genetic factors are crucial in pathogenesis in at least 20% of infertile men. In the proposed project we wish to investigate the influence of different types of genetic abnormalities to male infertility. The study of chromosomal abnormalities, Y chromosome microdeletions, selected Mendelian inherited disorders and genetic variation in selected candidate genes is proposed. Chromosomal abnormalities are well known etiological factor in male infertility. We wish to investigate types and proportion of constitutive karyotype abnormalities in and further analyse cytogenetically sperm cells in infertile men. The pathogenetic relationship between Y chromosome deletions and male infertility has been proposed but not yet well understood. We propose to investigate the frequency, pattern, population characteristics as well as correlation between deletions of Y chromosome and phenotype of male infertility. Over 30 monogenic diseases have been associated with male subfertility. We plan to investigate the importance of mutations in genes responsible for cystic fibrosis, myotonic dystrophy and Kennedy syndrome in male infertility. In addition to genetic defects which contribute qualitatively to male infertility, we hypothesise that genetic variation in certain genes could influence spermatogenesis quantitatively. Genetic polymorphisms in angiotensin convertase enzyme and ApoB genes were selected to test for association with male infertility as animal knock out experiments demonstrated importance of these genes in male fertility. In conclusion, we propose a study of genetic contribution to male infertility which could contribute to our understanding of spermatogenesis on one hand and improve clinical evaluation and therapy of male infertility.