Grant: Operating Grant: Boy's and Men's Health

Infertility is regarded as a major health problem, affecting approximately one in six couples in Canada. It is estimated that 30-40% of couples seeking fertility treatments are diagnosed with male-factor infertility due to abnormal sperm production. In the majority of these cases, the cause of infertility remains unknown. It is suspected that genetic and epigenetic factors may both play an important role in the onset of male infertility. 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. There is increasing evidence in the literature to suggest that infertile men may be at risk of having abnormal DNA methylation (a chemical modification of genetic sequences) in their sperm, which may affect sperm production. Recently, we also found that a subgroup of infertile men had increased imprinting defects (defects in the methylation of specific DNA sequences) in their sperm. We will use recently developed techniques to further characterize the meiotic defects that lead to the production of aneuploid sperm and male infertility in two unique infertile male groups (men with very low sperm counts with and without chromosome rearrangements). We will also investigate the prevalence of imprinting defects among infertile men, and its possible association with meiotic errors within the same study population. Detailed meiotic and imprinting studies of infertile men will begin to reveal the underlying genetic causes of male infertility. The results of this study could lead to improved treatment and reproductive outcomes for couples undergoing infertility treatments, such as intracytoplasmic sperm injection (ICSI).