Male germ cell development: turning on the apoptotic pathways

From the viewpoint of improving germ cell production and treatment of testicular cancers, understanding the control of testicular cell death is of great relevance. One of the prominent features of spermatogenesis is apoptosis of germ cells at different stages of differentiation, by which excess and unfit cells are discarded to maintain proper tissue homeostasis. A phase of heightened apoptosis known as the 'first wave of spermatogenesis' occurs when the gonocytes differentiate into spermatogonia. The germ cells use an extrinsic pathway of apoptosis involving the Fas/FasL molecules as well as the mitochondrial pathway of death using the Bcl-2 family of proteins. A comprehensive view of the involvement of the different pro- and anti-apoptotic molecules has been defined through the use of mutant and knockout mice and toxin-induced cell death models. In addition, hormones such as estrogens in the male are of great interest. The presence of estrogen receptors on germ cells makes these cells susceptible to environmental agents which can mimic estrogens and potentially cause functional impairment of the male gamete. Post-industrialization, an increase in testicular cancers has been recorded and carcinoma of germ cell origin is susceptible to platinum-based compounds that induce multiple apoptotic pathways. This review covers recent progress made on the above issues. The challenge is now to identify the precise signaling pathways and the mechanisms by which germ cells and germ cell tumors initiate cell death processes, and to utilize this information for improving reproductive health related issues.