Medical College, Guangxi University, Nanning, Guangxi, 530004, China.
Center Translational Medicine Research, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, 530011, China.
Toxicon. 2023 Jan 1;221:106964. doi: 10.1016/j.toxicon.2022.106964. Epub 2022 Nov 11.
Triptolide is a major active ingredient isolated from the traditional Chinese medicine Tripterygium wilfordii, which has anti-inflammatory, anti-cancer, and immunomodulatory effects. However, in clinical studies, triptolide has toxic side effects on the heart, kidney, liver and reproductive organs. With respect to female reproductive toxicity, damaging effects of triptolide on the ovary have been reported, but it has remained unknown whether oocytes are affected by triptolide. Therefore, this study established a concentration gradient of triptolide exposure in mice using 0 (control), 30, 60, and 90 μg triptolide/kg body weight/day administered by gavage. Triptolide administration for 28 d reduced body weight and ovarian weight and affected the developmental potential of oocytes. The triptolide-treated group exhibited meiotic failure of oocytes due to impaired spindle assembly, chromosome alignment, and tubulin stability. Triptolide was also found to induce mitochondrial dysfunction, autophagy and early apoptosis, iron homeostasis, and abnormal histone modifications. These adverse effects could be associated with oxidative stress induced by triptolide. In conclusion, our findings suggest detrimental effects of triptolide on mouse oocytes and, thus, on female reproduction.
雷公藤红素是从传统中药雷公藤中分离得到的主要活性成分，具有抗炎、抗癌和免疫调节作用。然而，在临床研究中，雷公藤红素对心脏、肾脏、肝脏和生殖器官有有毒的副作用。关于女性生殖毒性，已有报道称雷公藤红素对卵巢有损害作用，但尚不清楚卵母细胞是否受到雷公藤红素的影响。因此，本研究采用灌胃法建立了 0（对照）、30、60 和 90μg 雷公藤红素/公斤体重/天的浓度梯度，在小鼠中暴露于雷公藤红素。雷公藤红素处理 28 天导致体重和卵巢重量减轻，并影响卵母细胞的发育潜能。雷公藤红素处理组由于纺锤体组装、染色体排列和微管稳定性受损而导致卵母细胞减数分裂失败。雷公藤红素还可诱导线粒体功能障碍、自噬和早期凋亡、铁稳态和异常组蛋白修饰。这些不良反应可能与雷公藤红素诱导的氧化应激有关。总之，我们的研究结果表明雷公藤红素对小鼠卵母细胞有不良影响，进而对女性生殖功能有不良影响。
