Obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist, has been demonstrated to ameliorate the histopathological characteristics of liver damage. Nonetheless, the systemic safety profile of OCA with regard to reproduction and development remains poorly understood. In the present study, we conducted a dose–response experiment by administering OCA at doses of 5 mg/kg, 10 mg/kg, or 20 mg/kg through tube feeding to investigate its effect on reproductive development and fertilization rate in both male and female mice. Furthermore, we evaluated the levels of protein and mitochondrial function in the placenta through western blot, qPCR, and scanning electron microscopy. The results showed that 10 mg/kg and 20 mg/kg OCA doses significantly reduced the rate of placental implantation (P < 0.05). Also, OCA increased maternal body weight. In addition, OCA increased levels of FXR and TGR5 and produced changes in oxidative stress levels (P < 0.05). Mitochondrial activity result found that 10 mg/kg and 20 mg/kg of OCA significantly reduced the mitophagy autosomes/nucleus compared with the normal control group (P < 0.05). What is more, there was no significant difference in sperm count after OCA intervention in either C57BL/10 mice or BALB/c mice. Overall, we demonstrated that OCA treatment protected against placental implantation by suppressing placental oxidative stress and mitochondrial activity.

奥贝胆酸 (OCA) 是一种法尼醇 X 受体 (FXR) 激动剂，已被证明可以改善肝损伤的组织病理学特征。尽管如此，OCA 在生殖和发育方面的系统安全性仍然知之甚少。在本研究中，我们进行了剂量反应实验，通过管饲给予 OCA 5 mg/kg、10 mg/kg 或 20 mg/kg 的剂量，以研究其对雄性和雌性生殖发育和受精率的影响。雌性小鼠。此外，我们通过蛋白质印迹、qPCR 和扫描电子显微镜评估了胎盘中的蛋白质和线粒体功能水平。结果显示，10 mg/kg和20 mg/kg OCA剂量显着降低胎盘着床率（P < 0.05）。此外，OCA 还增加了母亲的体重。此外，OCA 还增加了 FXR 和 TGR5 的水平，并导致氧化应激水平发生变化（P < 0.05）。线粒体活性结果发现，与正常对照组相比，10 mg/kg和20 mg/kg OCA显着降低了线粒体自噬常染色体/细胞核（P < 0.05）。更重要的是，OCA 干预后，C57BL/10 小鼠和 BALB/c 小鼠的精子数量没有显着差异。总体而言，我们证明 OCA 治疗通过抑制胎盘氧化应激和线粒体活性来防止胎盘着床。