RhoGDIα regulates spermatogenesis through Rac1/cofilin/F-actin signaling

Commun Biol. 2023 Feb 23;6(1):214. doi: 10.1038/s42003-023-04579-7.

Abstract

Spermatogenesis is an extremely complex process, and any obstruction can cause male infertility. RhoGDIα has been identified as a risk of male sterility. In this study, we generate RhoGDIα knockout mice, and find that the males have severely low fertility. The testes from RhoGDIα-/- mice are smaller than that in WT mice. The numbers of spermatogonia and spermatocytes are decreased in RhoGDIα-/- testis. Spermatogenesis is compromised, and spermatocyte meiosis is arrested at zygotene stage in RhoGDIα-/- mice. Acrosome dysplasia is also observed in sperms of the mutant mice. At the molecular level, RhoGDIα deficiency activate the LIMK/cofilin signaling pathway, inhibiting F-actin depolymerization, impairing testis and inducing low fertility in mouse. In addition, the treatment of RhoGDIα-/- mice with Rac1 inhibitor NSC23766 alleviate testis injury and improve sperm quality by inhibiting the LIMK/cofilin/F-actin pathway during spermatogenesis. Together, these findings reveal a previously unrecognized RhoGDIα/Rac1/F-actin-dependent mechanism involved in spermatogenesis and male fertility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Depolymerizing Factors / metabolism
  • Actins* / metabolism
  • Animals
  • Infertility, Male* / genetics
  • Male
  • Mice
  • Mice, Knockout
  • Semen / metabolism
  • Signal Transduction / physiology
  • Spermatogenesis
  • rac1 GTP-Binding Protein / genetics
  • rho Guanine Nucleotide Dissociation Inhibitor alpha* / genetics
  • rho Guanine Nucleotide Dissociation Inhibitor alpha* / metabolism

Substances

  • Actin Depolymerizing Factors
  • Actins
  • rac1 GTP-Binding Protein
  • rho Guanine Nucleotide Dissociation Inhibitor alpha