Distinct Roles for Rac1 in Sertoli Cell Function during Testicular Development and Spermatogenesis

• Published in: Cell reports (Cambridge) Vol. 31; no. 2; p. 107513
• Main Authors: Heinrich, Anna, Potter, Sarah J., Guo, Li, Ratner, Nancy, DeFalco, Tony
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14.04.2020
• Subjects: Animals; blood-testis barrier; Cell Differentiation - physiology; cell polarity; Cell Polarity - physiology; ectoplasmic specialization; Male; Mice; Mice, Inbred C57BL; Neuropeptides - genetics; Neuropeptides - metabolism; RAC1; rac1 GTP-Binding Protein - genetics; rac1 GTP-Binding Protein - metabolism; Seminiferous Tubules - cytology; Sertoli cell; Sertoli Cells - cytology; Sertoli Cells - metabolism; Sertoli Cells - pathology; Spermatids - physiology; spermatogenesis; Spermatogenesis - genetics; Spermatogenesis - physiology; Spermatogonia - physiology; Testis - cytology; Testis - growth & development; spermatogenesis; Sertoli cell; ectoplasmic specialization; RAC1; cell polarity; blood-testis barrier
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.03.077

Sertoli cells are supporting cells of the testicular seminiferous tubules, which provide a nurturing environment for spermatogenesis. Adult Sertoli cells are polarized so that they can simultaneously support earlier-stage spermatogenic cells (e.g., spermatogonia) basally and later-stage cells (e.g., spermatids) apically. To test the consequences of disrupting cell polarity in Sertoli cells, we perform a Sertoli-specific conditional deletion of Rac1, which encodes a Rho GTPase required for apicobasal cell polarity. Rac1 conditional knockout adults exhibit spermatogenic arrest at the round spermatid stage, with severe disruption of Sertoli cell polarity, and show increased germline and Sertoli cell apoptosis. Thus, Sertoli Rac1 function is critical for the progression of spermatogenesis but, surprisingly, is dispensable for fetal testicular development, adult maintenance of undifferentiated spermatogonia, and meiotic entry. Our data indicate that Sertoli Rac1 function is required only for certain aspects of spermatogenesis and reveal that there are distinct requirements for cell polarity during cellular differentiation. [Display omitted] •Sertoli Rac1 function is required for later stages of spermatogenesis•Rac1-deficient Sertoli cells exhibit severe defects in apicobasal cell polarity•Rac1 is dispensable for testis differentiation and germline stem cell maintenance•Fetal Sertoli cells do not yet show hallmarks of complete apicobasal cell polarity Testicular Sertoli cells are polarized supporting cells that simultaneously support germ cells at various stages of differentiation. Heinrich et al. use a Sertoli-specific conditional deletion of Rac1, a Rho GTPase required for apicobasal cell polarity, to reveal the distinct requirements for Sertoli cell polarity during testicular differentiation and function.