Trichostatin A alleviated ovarian tissue damage caused by cigarette smoke exposure

Cigarette smoke (CS) has a negative impact on women's health and fertility. Studies have shown that histone deacetylases 1 and 2 (HDAC1/2) were involved in oocyte development. However, the roles of HDAC1/2 in ovarian toxicity caused by CS exposure and the therapeutic potential of trichostatin A (TSA, a HDAC inhibitor) for ovarian tissue damage have not been investigated. In this study, Female C57BL/6 mice were exposed to CS from six cigarettes mixed with indoor air for 120 min (one cigarette for 20 min) using a whole-body mainstream smoke exposure system twice daily for 30 days. TSA (0.6 mg/kg body weight) was injected intraperitoneally into mice in the Control TSA group and CS TSA group every two days for 30 days. We found that exposure to CS resulted in ovarian tissue damage and HDAC1/2 over-expression. TSA alleviated the structural changes of ovarian tissue induced by smoking and prevented the activation of HDAC1/2. Exposure to CS caused autophagy inhibition and pyroptosis activation. TSA treatment restored the expression of autophagy-associated proteins and decreased the levels of pyroptosis-related proteins induced by CS exposure. The TSA effect may be mediated by inhibition of HDAC1/2 involved in autophagy and pyroptosis process.