Grant: Operating Grant

Male infertility occurs in 9% of couples, frequently with unknown causes, leading to excessive use of assisted reproductive technology despite the possible negative health consequences on the children born. Research to find bio-indices of male fertility is greatly needed. Seminolipid (aka SGG), present at a high level in mammalian male germ cells, is essential for development in the testis, as shown in experimental animals. SGG on mature sperm is also important for fertilization. We have recently shown that homeostasis (balanced levels) of SGG in testes, as regulated by Sertoli cells, is relevant for sperm production and sperm fertilizing ability, especially in older males (40 years in men). Sertoli cells are oblong somatic cells spanning the tubules in the testis, where sperm are produced. Tight junctions at the basal part of the tubules exist between adjacent Sertoli cells, forming a barrier that excludes blood components from entering the compartment above. Developing germ cells are in this compartment and nourished by nutrients secreted from Sertoli cells. Sertoli cells also 'clean up' germ cells that have undergone apoptosis (programmed death), which occurs at a high rate in normal testis. Certain molecules of apoptotic cells, when existing at high amounts, are toxic to Sertoli cells, and need to be degraded in their lysosomes (organelles with degradation enzymes). SGG is one such molecule that has to be degraded by arylsulfatase A in Sertoli cell lysosomes. The failure of this degradation leads to 'lysosomal storage disorder' in Sertoli cells and subsequently a disability to support germ cell development. Production of good-quality sperm is also compromised in older males. Our proposed research will provide a better understanding of the significance of SGG homeostasis in male fertility. As well, SGG levels of sperm from fertile and infertile men will be determined, so that a threshold index will be obtained for diagnosis of male infertilit