Cdc42 activity in Sertoli cells is essential for maintenance of spermatogenesis

Sertoli cells are highly polarized testicular supporting cells that simultaneously nurture multiple stages of germ cells during spermatogenesis. Proper localization of polarity protein complexes within Sertoli cells, including those responsible for blood-testis barrier formation, is vital for spermatogenesis. However, the mechanisms and developmental timing that underlie Sertoli cell polarity are poorly understood. We investigate this aspect of testicular function by conditionally deleting Cdc42, encoding a Rho GTPase involved in regulating cell polarity, specifically in Sertoli cells. Sertoli Cdc42 deletion leads to increased apoptosis and disrupted polarity of juvenile and adult testes but does not affect fetal and postnatal testicular development. The onset of the first wave of spermatogenesis occurs normally, but it fails to progress past round spermatid stages, and by young adulthood, conditional knockout males exhibit a complete loss of spermatogenic cells. These findings demonstrate that Cdc42 is essential for Sertoli cell polarity and for maintaining steady-state sperm production. [Display omitted] •Cdc42 function in Sertoli cells is required for steady-state spermatogenesis•Sertoli Cdc42 is dispensable for fetal and early postnatal testis development•Loss of Cdc42 disrupts Sertoli cell polarity and blood-testis barrier function•CDC42-mediated Sertoli cell polarity is required starting in juvenile stages Sertoli cells of the testicular seminiferous tubule must be highly polarized to simultaneously sustain multiple stages of germ cells during spermatogenesis. Heinrich et al. use a Sertoli-specific conditional deletion mouse model to address the roles of CDC42-mediated apicobasal cell polarity in promoting testis development and spermatogenesis.