Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, Shenyang, 110004, China; Medical Research Center of Shengjing Hospital, China Medical University, Shenyang, 110004, China; Key Laboratory of Research and Application of Animal Model for Environmental and Metabolic Diseases, Liaoning Province, China.
Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, Shenyang, 110004, China; Medical Research Center of Shengjing Hospital, China Medical University, Shenyang, 110004, China.
Reprod Toxicol. 2020 Apr;93:89-98. doi: 10.1016/j.reprotox.2020.01.006. Epub 2020 Jan 24.
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.
香烟烟雾（CS）对女性健康和生育能力有负面影响。研究表明，组蛋白去乙酰化酶 1 和 2（HDAC1/2）参与卵母细胞的发育。然而，CS 暴露引起的卵巢毒性中 HDAC1/2 的作用以及 Trichostatin A（TSA，一种 HDAC 抑制剂）治疗卵巢组织损伤的潜力尚未得到研究。在这项研究中，雌性 C57BL/6 小鼠使用全身主流烟雾暴露系统每天两次暴露于与室内空气混合的六支香烟的 CS 中 120 分钟（一支香烟 20 分钟），共 30 天。TSA（0.6mg/kg 体重）在对照组+TSA 组和 CS+TSA 组的小鼠中每两天腹膜内注射一次，共 30 天。我们发现，CS 暴露导致卵巢组织损伤和 HDAC1/2 过表达。TSA 缓解了吸烟引起的卵巢组织结构变化，并阻止了 HDAC1/2 的激活。CS 暴露导致自噬抑制和细胞焦亡激活。TSA 处理恢复了自噬相关蛋白的表达，并降低了 CS 暴露诱导的细胞焦亡相关蛋白的水平。TSA 的作用可能是通过抑制参与自噬和细胞焦亡过程的 HDAC1/2 介导的。
