Aromatase, Estrogens and Testicular Germ Cell Development

Abstract

Aromatase converts irreversibly androgens into estrogens and is present in the endoplasmic reticulum of various tissues including the mammalian testis. In most of the mammals studied up today, at least in rodents, all testicular cells except peritubular cells express aromatase. Indeed in adult rat germ cells (pachytene spermatocytes and round spermatids) we have demonstrated- the presence of a functional aromatase - and the estrogens output is equivalent to that of Leydig cells. Moreover in the adult rat, transcripts of aromatase vary according to the germ cell type and to the stages of seminiferous epithelium, a maximum being observed at stage I. By contrast with the androgen receptors mainly localized in somatic cells, estrogen receptors (ERs) are described in most of the testicular cells including germ cells. Both estrogen receptors mRNA at levels are higher in purified round spermatids than in pachytene spermatocytes suggesting a putative role of estrogens in the haploid steps of spermatogenesis. Thus, besides the presence of high affinity ERα and/or ERβ, a rapid membrane effect has been recently reported in mouse testis leading to a control of mouse cell proliferation by estradiol. In a recent work we demonstrated that GPR30 (a transmembrane intracellular estrogen receptor) is expressed in adult rat pachytene spermatocytes and that estrogens through both GPR30 and ERα are able to activate the rapid EGFR/ERK/c-jun signaling cascade, which in turn triggers an apoptotic mitochondrial pathway involving an increase in Bax expression and a concomitant reduction of cyclin A1 and B1 gene levels which are involved in the balance between cellular proliferation and apoptosis. As already demonstrated in ArKO mice and from the data collected in ERαKO, estrogens do play an important role in germ cells development and maturation. Thus the role of estrogens (intracrine, autocrine and / or paracrine) in spermatogenesis (proliferation, apoptosis, survival and maturation) and more generally, the male reproduction is now obvious.