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

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.

Sexual antagonism and sex determination in three syngnathid species alongside a male pregnancy gradient

“…The third overrepresented pathway – “Signaling by Rho GTPases” is involved in many cellular processes and helps cells to respond to external and internal stimuli via Rho GTPases – a family of molecular-switch proteins (G proteins) (Bar-Sagi and Hall 2000; Jaffe and Hall 2005; Hodge and Ridley 2016; Perry and Maddox 2019; Boueid et al 2020). Several members of the G proteins family were found to be crucial for spermatogenesis (as examined in mammals) (Lui et al 2003; Zhang et al 2010; Zhu et al 2023). Processes related to noncoding RNAs (ncRNA metabolic process and ncRNA processing) were found to be influenced by DEA between sexes in all species.…”

“…Anon 2022; Mattick et al 2023). A plethora of reports discuss effects of regulatory ncRNA expression between the sexes on development, physiology, immunity and disease (Zhou et al 2014;Gershoni and Pietrokovski 2017;Zhang et al 2017;Gal-Oz et al 2019;Rosspopoff et al 2023a;Wang et al 2023). A known role of ncRNA roles in sexual development is the inactivation of the with XIST in humans and other placental mammals (Brown et al 1991;Lee et al 1999;Dupont and Gribnau 2013;Posynick and Brown 2019;Rosspopoff et al 2023b).…”

“…GTPases" is involved in many cellular processes and helps cells to respond to external and 2020). Several members of the G proteins family were found to be crucial for spermatogenesis (as examined in mammals) (Lui et al 2003;Zhang et al 2010;Zhu et al 2023).…”

“…The third overrepresented pathway -"Signaling by Rho GTPases" -is involved in many cellular processes and helps cells to respond to external and internal stimuli via Rho GTPases -a family of molecular-switch proteins (G proteins) (Bar-Sagi and Hall 2000; Jaffe and Hall 2005;Hodge and Ridley 2016;Perry and Maddox 2019;Boueid et al 2020). The overrepresentation of this pathway could be related to reproduction as several members of the family were found to be crucial for spermatogenesis (as examined in mammals) (Lui et al 2003;Zhang et al 2010;Zhu et al 2023).…”

Gss deficiency causes age-related fertility impairment via ROS-triggered ferroptosis in the testes of mice

“…Male infertility is a multifactorial pathological condition that affects approximately 7% of the male population, and is primarily attributed to impaired spermatogenesis [ 1 , 2 ]. Spermatogenesis begins with spermatogonia cells derived from spermatogonial stem cells, and progresses from the basal lamina towards the lumen of the seminiferous tubules [ 3 ]. Spermatogonia differentiate into spermatocytes, and then spermatocytes meiosis into round spermatids.…”