Cheng Si-Yao, Yang Yi-Fan, Wang Ya-Long, Yue Zhao-Ping, Chen Yan-Zhu, Wang Wen-Ke, Xu Zhi-Ran, Li Lin-Feng, Shen Hao, Qi Zhi-Min, Xu Chang-Long, Liu Yu
Medical College, Guangxi University, Nanning, Guangxi, 530004, China.
Center for Reproductive Medicine, Maternity and Child Health Care Hospital in Xiangtan, Hunan, 411100, China.
Food Chem Toxicol. 2025 Feb;196:115201. doi: 10.1016/j.fct.2024.115201. Epub 2024 Dec 12.
Triptolide (TPL), a prominent bioactive constituent derived from the Chinese herb Tripterygium wilfordii, exhibits diverse pharmacological effects such as anti-tumor and anti-immune properties. Despite its extensive clinical application for the treatment of arthritis and immune disorders, TPL has been associated with multiorgan toxicity, including adverse effects on the female reproductive system. However, the precise mechanisms underlying TPL-induced ovarian damage remain poorly understood. In this study, employing a mouse toxicological model, exposure to TPL was observed to result in decreased ovarian coefficient and fertility. Subsequent research demonstrated TPL exposure affected mitochondrial function, increased mitochondrial outer membrane permeability, resulted in mtDNA releasing into the cytoplasm. These events subsequently activated cGAS-STING pathway, leading to ovarian inflammation. Furthermore, TPL exposure has been found to disrupt the meiotic maturation of oocytes, which is mechanistically associated with suboptimal morphology of spindle and microtubule organizing centers (MTOCs). This association has been further confirmed through the use of reduced representation bisulfite sequencing (RRBS). In conclusion, our study demonstrates that TPL exposure can hinder follicular development, resulting in ovarian inflammation and reduced oocyte quality.
雷公藤甲素（TPL）是从中药雷公藤中提取的一种重要生物活性成分，具有多种药理作用，如抗肿瘤和免疫调节特性。尽管TPL在治疗关节炎和免疫紊乱方面有广泛的临床应用，但它与多器官毒性有关，包括对女性生殖系统的不良影响。然而，TPL诱导卵巢损伤的确切机制仍不清楚。在本研究中，采用小鼠毒理学模型，观察到暴露于TPL会导致卵巢系数和生育力下降。随后的研究表明，TPL暴露影响线粒体功能，增加线粒体外膜通透性，导致线粒体DNA释放到细胞质中。这些事件随后激活cGAS-STING通路，导致卵巢炎症。此外，已发现TPL暴露会破坏卵母细胞的减数分裂成熟，这在机制上与纺锤体和微管组织中心（MTOC）的形态不佳有关。通过使用简化代表性亚硫酸氢盐测序（RRBS）进一步证实了这种关联。总之，我们的研究表明，TPL暴露会阻碍卵泡发育，导致卵巢炎症和卵母细胞质量下降。
