Accumulation Of Seminolipid In Sertoli Cells Is Associated With Increased Levels Of Reactive Oxygen Species And Male Subfertility: Studies In Aging Arsa Null Male Mice

Seminolipid (also known as sulfogalactosylglycerolipid-SGG), present selectively in male germ cells, plays important roles in spermatogenesis and sperm-egg interaction. The proper degradation of SGG in apoptotic germ cells is also as important. Sertoli cells first phagocytose apoptotic germ cells, then Sertoli lysosomal arylsulfatase A (ARSA) desulfates SGG, the first step of SGG degradation. We have reported that aging male Arsa(-/-) mice become subfertile with SGG accumulation in Sertoli cell lysosomes, typical of a lysosomal storage disorder (LSD). Since reactive oxygen species (ROS) levels are increased in other glycolipid-accumulated LSDs, we quantified ROS in Arsa(-/-) Sertoli cells. Our analyses indicated increases in superoxide and H2O2 in Arsa(-/-) Sertoli cells with elevated apoptosis rates, relative to WT counterparts. Excess H2O2 from Arsa(-/-) Sertoli cells could travel into testicular germ cells (TGCs) to induce ROS production. Our results indeed indicated higher superoxide levels in Arsa(-/-) TGCs, compared with WT TGCs. Increased ROS levels in Arsa(-/-) Sertoli cells and TGCs likely caused the decrease in spermatogenesis and increased the abnormal sperm population in aging Arsa(-/-) mice, including the 50% decrease in sperm SGG with egg binding ability. In summary, our study indicated that increased ROS production was the mechanism through which subfertility manifested following SGG accumulation in Sertoli cells.