Genetics of Male Infertility

Abstract

Background: Male infertility is a common condition that affects at least 7% of men in Western countries and is associated with an elevated risk of comorbidities and mortality. While genetics is predicted to play a role in a significant percentage of cases, the aetiology of male infertility remains largely unknown. In light of this, the International Male Infertility Genomics Consortium (IMIGC) was founded, with the goals of recruiting large cohorts of infertile men, use next generation sequencing to identify high-confidence genetic causes of their infertility, and validate these genetic causes using replication studies and/or animal models. A number of working groups within the IMIGC are beginning to identify several novel genetic variants causative of human male infertility, and thus, essential male fertility genes. The requirement of these poorly characterised genes for male fertility is being further tested in mice and flies, including the identification of their molecular function(s) across the discrete phases of spermatogenesis and sperm function. These studies will ultimately transform the diagnosis of male infertility from a phenotypic description to a molecular diagnosis. These findings will also allow more realistic predictions regarding the consequences of using gametes from men with genetic variants in assisted reproductive technologies, and will likely identify avenues for therapeutic intervention.