Abstract

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 (H 2 S), 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 H 2 S-synthesizing enzyme cystathionine γ-lyase (CSE), while significantly suppressed by H 2 S donor Sodium hydrosulfide (NaHS). It was also attenuated by Tanshinone IIA (Tan IIA), an active ingredient of Danshen that stimulated H 2 S production in Sertoli cells. Apart from Sertoli cells, H 2 S also protected the cultured germ cells from ACR-initiated cell death. Collectively, our study characterized H 2 S as endogenous defensive mechanism against ACR in Sertoli cells and germ cells. This property of H 2 S could be used to prevent and treat ACR-related reproductive injury.