Grant: Operating Grant

It is estimated that 2% of men are infertile due to severe defects in sperm production. In the majority of these cases, the cause of infertility remains unknown. During spermatogenesis, cells must undergo a specialized type of cell division known as meiosis. Recent studies have shown that errors in this meiotic division are more prevalent in infertile men and may play an important role in idiopathic male infertility. We recently provided evidence that meiotic errors in infertile men may also be associated with the production of aneuploid sperm, that is, sperm containing either extra or missing chromosomes. Our prelimineary results suggest that meiotic errors may lead to arrest in some cells, leading to infertility, while other cells may proceed through meiosis and produce aneuploid sperm. We are using recently developed techniques to further charaterize the meiotic defects that lead to the production of aneuploid sperm and male infertility. Such information could eventually aid in risk assessment for men undergoing assisted reproductive technologies (ART). Aneuploidy remains the most frequent cause of miscarriage, and, among liveborns, it is the most common genetic cause of congenital malformations. The results of this study will also provide further direction in the search for gene mutations that contribute to male-factor infertility.