Origin and function of embryonic Sertoli cells

In the adult testis, Sertoli cells (SCs) are the epithelial supporting cells of the seminiferous tubules that provide germ cells (GCs) with the required nutrients and structural and regulatory support to complete spermatogenesis. SCs also form the blood-testis barrier, phagocytose apoptotic spermatocytes and cell debris derived from spermiogenesis, and produce and secrete numerous paracrine and endocrine signals involved in different regulatory processes. In addition to their essential functions in the adult testis, SCs play a pivotal role during testis development. They are the first cells to differentiate in the embryonic XY gonadal primordium and are involved in the regulation of testis-specific differentiation processes, such as prevention of GC entry into meiosis, Leydig and peritubular myoid cell differentiation, and regression of the Müllerian duct, the anlagen of the uterus, oviducts, and the upper part of the vagina. Expression of the Y-linked gene SRY in pre-SCs initiates a genetic cascade that leads to SC differentiation and subsequently to testis development. Since the identification of the SRY gene, many Sertoli-specific transcription factors and signals underlying the molecular mechanisms of early testis differentiation have been identified. Here, we review the state of the art of the molecular interactions that commit the supporting cell lineage of the gonadal primordium to differentiate as SCs and the subsequent Sertoli-specific signaling pathways involved in early testis differentiation.