Levels of Leydig cell autophagy regulate the fertility of male naked mole-rats

Abstract

Fertility is abolished in nonbreeding males in colonies of natal naked mole-rats (NMRs). Although spermatogenesis occurs in both breeding and nonbreeding male NMRs, the mechanisms underlying the differences in fertility between breeders and nonbreeders remain unexplored. In this study, a significant decrease in autophagy was observed in Leydig cells of the testis from nonbreeding male NMRs. This alteration was visualised as a significant decrease in the levels of autophagy-related gene 7 (Atg7), Atg5, microtubule-associated protein 1A/B light chain 3 (LC3-II/I) and the number of autophagosomes and an increase in P62 levels using Western blotting analyses. Furthermore, monodansylcadaverine (MDC) staining and Western blot analyses revealed that testosterone production decreased in nonbreeding male NMR Leydig cells, this decrease was associated with a reduction in autophagy. Primary Leydig cells from breeding and nonbreeding male NMRs were processed to investigate the effect of an autophagy inhibitor (3-MA, 3-methyladenine) or an autophagy activator (rapamycin) on testosterone production. Rapamycin induced an increase in testosterone production in NMR Leydig cells, whereas 3-MA had the opposite effect. Consequently, spermatogenesis, the weight of the testis, and androgen levels were dramatically reduced in nonbreeding male NMRs. While rapamycin treatment restored the fertility of nonbreeding male NMRs. Based on these results, inadequate autophagy correlates with a decrease in steroid production in nonbreeding male NMR Leydig cells, which may ultimately influence the spermatogenesis and fertilities of these animals.

Autophagy as a consequence of seasonal functions of testis and epididymis in adult male European bison (Bison bonasus, Linnaeus 1758)

“…It was previously demonstrated in mice that mTOR is needed to differentiate spermatogonia (Busada et al 2015a;Busada et al 2015b). Also, the study by Sahin et al (2018) suggested a role of the mTOR pathway in meiotic progress of male germ cells (Sahin et al 2018), and it was shown earlier that changes in the autophagy activity can affect steroid secretion by Leydig cells (Lin and Baehrecke 2015;Yang et al 2017;Yi and Tang 1995). On the basis of our results, we can suggest that high expression of Atg5 in the testis in September may be associated with spermatogenesis.…”

Taurine induces autophagy and inhibits oxidative stress in mice Leydig cells

“…The reducing testosterone level in 3-MA- treated cells indicated autophagy involved in testosterone production in the TM3 cells. Rapamycin (autophagy stimulator) induced an increase in testosterone concentration in rat Leydig cells, whereas 3-MA had the opposite effect ( Yang et al ., 2017 ).…”

EGFR Signaling Stimulates Autophagy to Regulate Stem Cell Maintenance and Lipid Homeostasis in the Drosophila Testis

“…However, recent evidence has revealed an underappreciated role for basal levels of autophagy in the maintenance of cellular and tissue homeostasis. Dysregulation of autophagy is associated with age-related pathologies, such as neurological disorders ( Lynch-Day et al, 2012 ; Zare-Shahabadi et al, 2015 ; Rubinsztein et al, 2005 ) and cancer ( Saito et al, 1993 ; Gao et al, 1995 ), and loss of autophagic activity has been shown to impact male fertility ( Yang et al, 2017 ; Liu et al, 2016 ). Given the role of stem cells in maintaining tissue homeostasis throughout life, quality-control mechanisms are also important to ensure proper stem cell function ( Guan et al, 2013 ).…”