Investigating the Role of Genome Instability in Male Infertility

Infertility is a widespread condition affecting about 15% of couples worldwide, with a tendency to increase. Male factor is found in 50% cases of infertility, with increasing proportion of severe male infertility (oligoasthenoteratozoospermia - OAT) where artificial assisted reproduction techniques (ART) are used to achieve the pregnancy. In about 75% of the OAT causable factors are not found, and they remain unexplained. Genetic testing for karyotype and Y chromosome microdeletions is recommended in these cases, however, these aberrations are found only in 10-15% of the OAT cases. Also, the predicting factors from the male side for the outcome of the ART are lacking. Our hypothesis is that genome instability may be among the major causes for the severe male infertility. We aim to assess the genome instability in men with OAT by the novel markers: analysis of transcription of retrotransposons, PIWI/piRNA pathway, and pathogenic allelic variants in RAD51 and DMC1 mediated double-strand break repair system genes that play crucial role in spermatogenesis. The scientific objective of the project is to study the role of genome instability in severe male infertility, that in the future studies would serve as the basis for the development of a tool-kit based on the mentioned markers of the genome instability - that might predict the outcome of the ART procedures that still remains successful only in about 50% of cases, with no distinct predictive tests available from the male side.