Sphingolipid regulation of female gonadal cell apoptosis.

Ceramide and sphingosine-1-phosphate (S1P) are sphingosine-based lipid signaling molecules that have been implicated as key mediators of cellular growth, differentiation, and apoptosis. The cellular response depends on cell type, on the absence or presence of other signals initiated by the same or another stimulus, and on the subcellular location of sphingomyelin hydrolysis leading to ceramide generation. Consistent with mounting evidence implicating components of the sphingomyelin pathway as mediators of cellular life and death in nonreproductive tissues, recent data have indicated that sphingolipid-based signaling events are also prominent features of cellular development and apoptosis in the fetal and postnatal female gonads. This area of investigation represents a new research avenue of considerable significance for both basic biology and clinical medicine because of the massive levels of developmental death that occur normally in the female germ line, especially during gametogenesis, as well as of the central role of oocyte apoptosis in female gonadal failure resulting from pathologic insults.