The role of sphingolipid metabolism in female reproductive health disorders

Sphingolipids are bioactive lipids that regulate cell proliferation, differentiation, apoptosis, angiogenesis, and inflammation. In recent years, their role in maintaining the ovarian reserve and developing of female reproductive disorders has gained increasing attention. Ceramides (CERs) and sphingosine-1-phosphate (S1P) form a dynamic balance between pro-apoptotic and pro-survival signals, determining the fate of follicles and oocytes. Dysregulation of sphingolipid metabolism has been identified in ovarian cancer, polycystic ovary syndrome, endometriosis, obesity, diminished ovarian reserve, and premature ovarian insufficiency. These conditions are accompanied by a shift in the CERs/S1P ratio, which affects oocyte quality and their susceptibility to oxidative stress, chemotherapy, and inflammation. Emerging evidence indicates that targeted modulation of the sphingolipid pathway — including enzymes such as sphingosine kinases, ceramide synthases, sphingomyelinases, and ceramide transfer protein, as well as S1P receptors may represent a promising approach for preserving ovarian reserve, preventing infertility, and overcoming chemoresistance in ovarian cancer. S1P exhibits protective properties toward oocytes, whereas ceramide analogues and inhibitors of sphingolipid-metabolizing enzymes offer new opportunities for personalized therapy. Summarizing current data on sphingolipid metabolism in reproductive tissues highlights these molecules not only as biomarkers of pathology but also as potential therapeutic targets, which is particularly relevant for developing fertility-preserving strategies and improving the outcomes of gynecological disease treatment.

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