From Enrico Sertoli to freemartinism: the many phases of the master testis-determining cell†

Sertoli cells, first identified in the adult testis by Enrico Sertoli in the mid-nineteenth century, are known for their role in fostering male germ cell differentiation and production of mature sperm. It was not until the late twentieth century with the discovery of the testis-determining gene SRY that Sertoli cells' new function as the master regulator of testis formation and maleness was unveiled. Fetal Sertoli cells facilitate the establishment of seminiferous cords, induce appearance of androgen-producing Leydig cells, and cause regression of the female reproductive tracts. Originally thought be a terminally differentiated cell type, adult Sertoli cells, at least in the mouse, retain their plasticity and ability to transdifferentiate into the ovarian counterpart, granulosa cells. In this review, we capture the many phases of Sertoli cell differentiation from their fate specification in fetal life to fate maintenance in adulthood. We also introduce the discovery of a new phase of fetal Sertoli cell differentiation via autocrine/paracrine factors with the freemartin characteristics. There remains much to learn about this intriguing cell type that lay the foundation for the maleness.

Automated summary

Sertoli cells, first discovered in the adult testis in the mid-nineteenth century, play a crucial role in male germ cell differentiation and sperm production. Recent research has revealed that Sertoli cells also serve as a master regulator in testis formation and male development. They are involved in various processes, including establishment of seminiferous cords, induction of Leydig cells, and regression of the female reproductive tracts. Sertoli cells demonstrate plasticity and can transdifferentiate into granulosa cells in the ovary. Further studies are needed to fully understand the complexity of this cell type and its contribution to maleness.