The effects of hormone-mediated PI3K/AKT signaling on spermatogenesis in Sertoli cells

The phosphoinositide-3-kinase/Akt (PI3K/AKT) signaling pathway is crucial for Sertoli cell development and completing spermatogenesis. Its main role is to promote proliferation and inhibit apoptosis. Many factors activate the PI3K/AKT pathway, like hormones, such as follicle stimulating hormone (FSH), androgen, estrogen, insulin to name a few. Many of these factors have receptors inside or on the surface of Sertoli cells (SCs). This review summarizes how these hormones directly regulate the PI3K/AKT signaling pathway in SCs, which in turn affects SC proliferation and differentiation. Further, hormone-mediated PI3K/AKT signaling also stimulates SC secretion, which is essential for germ cell development, suggesting an indirect role of PI3K/AKT signaling during spermatogenesis. These functions include promoting spermatogonia proliferation and differentiation, meiosis of spermatocytes, sperm maturation, and their release. This review also provides potential hints for clinically treating male infertility issues like cryptorchidism and Sertoli cell-only syndrome.