Hydrogen sulfide protects Sertoli cells against toxicant Acrolein-induced cell injury

Acrolein (ACR), a highly toxic α,β-unsaturated aldehyde, is considered to be a common mediator behind the reproductive injury induced by various factors. However, the understanding of its reproductive toxicity and prevention in reproductive system is limited. Given that Sertoli cells provide the first-line defense against various toxicants and that dysfunction of Sertoli cell causes impaired spermatogenesis, we, therefore, examined ACR cytotoxicity in Sertoli cells and tested whether hydrogen sulfide (H₂S), a gaseous mediator with potent antioxidative actions, could have a protective effect. Exposure of Sertoli cells to ACR led to cell injury, as indicated by reactive oxygen species (ROS) generation, protein oxidation, P38 activation and ultimately cell death that was prevented by antioxidant N-acetylcysteine (NAC). Further studies revealed that ACR cytotoxicity on Sertoli cells was significantly exacerbated by the inhibition of H₂S-synthesizing enzyme cystathionine γ-lyase (CSE), while significantly suppressed by H₂S donor Sodium hydrosulfide (NaHS). It was also attenuated by Tanshinone IIA (Tan IIA), an active ingredient of Danshen that stimulated H₂S production in Sertoli cells. Apart from Sertoli cells, H₂S also protected the cultured germ cells from ACR-initiated cell death. Collectively, our study characterized H₂S as endogenous defensive mechanism against ACR in Sertoli cells and germ cells. This property of H₂S could be used to prevent and treat ACR-related reproductive injury.