Modulators of spermatogenic cell survival

Apoptosis is a process of cell suicide, the mechanisms of which are encoded in the chromosomes of all nucleated cells. Apoptosis occurs spontaneously throughout mammalian spermatogenesis for the development of normal mature spermatozoa and for the elimination of excess or abnormal germ cells: a critical prerequisite for functional spermatogenesis under physiological conditions. Any deregulation of the apoptotic process during spermatogenesis would lead to defective sperm formation and while increased apoptosis could potentially lead to infertility, decreased cell death could do the same by disrupting testicular homeostasis due to accumulation of cells. Male germ cell apoptosis occurs through two major pathways, involving either mitochondria (intrinsic) or cell surface death receptors (extrinsic). The mitochondrial pathway of apoptosis involves the Bcl-2 group of proteins and different members of this group are involved in diverse situations. The cell death receptor pathway involves members of the TNF receptor superfamily. The stimuli for germ cell apoptosis are internal cues that control proper homeostasis of the testicular tissue or external agents including testicular toxins, heat stress and chemotherapeutic agents. In addition, an imbalance of hormones can lead to the apoptosis of germ cells. The pathway of apoptosis adopted by the germ cells depends on the type of stimuli they receive. This review discusses the recent advances made in the understanding of the mechanisms of germ cell apoptosis that may provide clues to the control of male fertility or treating germ cell tumors and other testis associated pathological conditions.