Miao Liqing, Chen Mei, Zhou Yujia, Pan Shuangjia, Li Xiaosheng, Wang Yuexin, Zhang Jian'an, Zhu Xueqiong
Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Department of obstetrics and gynecology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Department of obstetrics and gynecology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Department of Obstetrics and Gynecology, Taizhou Women and Children's Hospital of Wenzhou Medical University, Zhejiang, China.
Cell Signal. 2025 Oct;134:111916. doi: 10.1016/j.cellsig.2025.111916. Epub 2025 Jun 4.
Propofol is widely used to induce and maintain anesthesia during gynecological surgery and assisted reproduction. However, few studies have investigated the influence of propofol on ovarian function and the related mechanism. In this study, propofol was administered to female mice, and ovarian function was evaluated by measuring serum AMH levels, follicle counts, and expression of related proteins. IOSE-80 and KGN cells were treated with propofol to assess mitochondrial function and mitophagy using fluorescence staining, ROS and mitochondrial membrane potential assays, and Western blotting. Recombinant TGF-β1 was applied both in vivo and in vitro to investigate the involvement of the TGF-β/SMAD2/3 signaling pathway. These results showed that propofol reduced the serum AMH level and the number of follicles in the mice ovaries, downregulated the protein expressions of FSHR and CYP19A1, and facilitated ovarian cell apoptosis both in vivo and in vitro. Treatment with propofol significantly decreased the mitochondrial fluorescence intensity and increased mitophagy fluorescence in IOSE-80 and KGN cells. Additionally, propofol enhanced ROS generation, decreased mitochondrial membrane potential and increased the levels of proteins associated with mitophagy (LC3B, PINK1, PARKIN). Propofol lessened the abundance of TGF-β1, SMAD2/3 and phosphorylated-SMAD2/3. Co-treatment with recombinant TGF-β1 significantly increased cell survival, reduced apoptosis, and upregulated the protein expression levels of FSHR, CYP19A1, PINK1, and PARKIN in IOSE-80 and KGN cells. These results demonstrated that propofol over-activates mitophagy through the TGF-β/SMAD2/3 pathway, and thus affects ovarian function. This finding provides some guidance for women with fertility needs when choosing anesthesia drugs for surgery.
丙泊酚广泛用于妇科手术和辅助生殖过程中的麻醉诱导和维持。然而，很少有研究探讨丙泊酚对卵巢功能的影响及其相关机制。在本研究中，对雌性小鼠给予丙泊酚，并通过测量血清抗缪勒管激素（AMH）水平、卵泡计数及相关蛋白表达来评估卵巢功能。用丙泊酚处理人卵巢表面上皮细胞系-80（IOSE-80）和人颗粒细胞系（KGN），通过荧光染色、活性氧（ROS）和线粒体膜电位检测以及蛋白质印迹法来评估线粒体功能和线粒体自噬。在体内和体外应用重组转化生长因子-β1（TGF-β1）来研究TGF-β/SMAD2/3信号通路的参与情况。这些结果表明，丙泊酚降低了小鼠卵巢血清AMH水平和卵泡数量，下调了促卵泡激素受体（FSHR）和细胞色素P450 19A1（CYP19A1）的蛋白表达，并在体内和体外促进卵巢细胞凋亡。丙泊酚处理显著降低了IOSE-80和KGN细胞中的线粒体荧光强度并增加了线粒体自噬荧光。此外，丙泊酚增强了ROS生成，降低了线粒体膜电位，并增加了与线粒体自噬相关蛋白（微管相关蛋白1轻链3β（LC3B）、无翅型MMTV整合位点家族成员1（PINK1）、帕金森病蛋白（PARKIN））的水平。丙泊酚降低了TGF-β1、SMAD2/3和磷酸化SMAD2/3的丰度。重组TGF-β1联合处理显著提高了IOSE-80和KGN细胞的存活率，减少了细胞凋亡，并上调了FSHR、CYP19A1、PINK1和PARKIN的蛋白表达水平。这些结果表明，丙泊酚通过TGF-β/SMAD2/3途径过度激活线粒体自噬，从而影响卵巢功能。这一发现为有生育需求的女性在选择手术麻醉药物时提供了一些指导。
