Sertoli cell modulates MAA-induced apoptosis of germ cells throughout voltage-operated calcium channels.

Abstract The aim of our study is to demonstrate that in the mammalian testis, Sertoli cells, which regulate germ cell proliferation and differentiation, are also involved in the control of germ cell apoptosis throughout voltage-operated calcium channels (VOCCs) and that the contacts between Sertoli cells and germ cells are necessary for such a modulation. As a marker of germ cell apoptosis, we chose clusterin, a ubiquitous glycoprotein synthesized by Sertoli cells, since it has been shown that Sertoli cell-derived clusterin is present in large amounts in dying germ cells, i.e., pachytene spermatocytes. We used methoxy acetic acid (MAA) as an inductor of in vitro germ cell apoptosis. Our main findings are: 1. In cultured rat Sertoli cells, clusterin expression is modulated by MAA; Sertoli cell VOCCs are involved in such a modulation 2. In cultured seminiferous tubules, Sertoli cell VOCC block prevents accumulation of clusterin in germ cells .As a consequence, the spermatocytes, although exposed to MAA, do not undergo apoptosis (Fig. 1). 3. Effects of VOCC blockers are strictly correlated to the integrity of seminiferous epithelium. Our results showing that methoxy acetic acid is ineffective on germ cells not in contact with Sertoli cells indicate that the junctions existing in the seminiferous epithelium between Sertoli cells and between Sertoli cells and germ cells are essential not only for allowing correct spermatogenesis, but also for the control of germ cell viability.