AUTHOR=O’Donnell Liza , Whiley Penny A. F. , Loveland Kate L. TITLE=Activin A and Sertoli Cells: Key to Fetal Testis Steroidogenesis JOURNAL=Frontiers in Endocrinology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.898876 DOI=10.3389/fendo.2022.898876 ISSN=1664-2392 ABSTRACT=

The long-standing knowledge that Sertoli cells determine fetal testosterone production levels is not widespread, despite being first reported over a decade ago in studies of mice. Hence any ongoing use of testosterone as a marker of Leydig cell function in fetal testes is inappropriate. By interrogating new scRNAseq data from human fetal testes, we demonstrate this situation is also likely to be true in humans. This has implications for understanding how disruptions to either or both Leydig and Sertoli cells during the in utero masculinization programming window may contribute to the increasing incidence of hypospadias, cryptorchidism, testicular germ cell tumours and adult infertility. We recently discovered that activin A levels directly govern androgen production in mouse Sertoli cells, because the enzymes that drive the conversion of the precursor androgen androstenedione to generate testosterone are produced exclusively in Sertoli cells in response to activin A. This minireview addresses the implications of this growing understanding of how in utero exposures affect fetal masculinization for future research on reproductive health, including during programming windows that may ultimately be relevant for organ development in males and females.