The regulation of male fertility by the PTPN11 tyrosine phosphatase.

PTPN11 (also known as SHP2) is a ubiquitously expressed non-receptor tyrosine phosphatase that regulates cell survival, proliferation, differentiation, migration and adhesion. Naturally occurring mutations in the PTPN11 gene cause Noonan and LEOPARD syndromes, two genetic disorders that are characterized by a spectrum of defects including male infertility. This review summarizes four cellular and molecular mechanisms by which PTPN11 acts to support male fertility. First, PTPN11 is required for the proliferation and survival of spermatogonial stem cells (SSCs) that are essential to replenish the germ cells that will become sperm. Second, PTPN11 regulation of cellular adhesion functions in Sertoli cells is required to maintain the blood-testis barrier (BTB) that protects meiotic and post-meiotic germ cells. Third, expression of PTPN11 in Sertoli cells is essential to prevent premature differentiation and exhaustion of the SSC population and to maintain the SSC niche. Finally, in Leydig cells, PTPN11 supports mitochondrial fusion and the expression of acyl-CoA synthetase (ACSL4) needed for the production of steroids including testosterone, which is required for fertility.