FIG. 9.

Upstream signaling pathway involved in germ cell apoptosis triggered by mild testicular hyperthermia or by hormonal deprivation. In both models the induction of apoptosis is triggered by a MAPK14-mediated pathway. Activation of MAPK14, through changes in the ratio of BAX and BCL2 in the mitochondria, triggers intrinsic pathway signaling and promotes germ cell apoptosis in response to a lack of hormonal stimulation [17]. The same signaling pathway is also the key pathway for heat-induced testicular germ cell apoptosis. However, unlike the hormone deprivation model, this signaling pathway promotes germ cell apoptosis by provoking BCL2 phosphorylation, leading to its inactivation, thereby resulting in the perturbation of the BAX/BCL2 rheostat and the subsequent activation of the mitochondria-dependent death pathway.