Obeticholic acid treatment of mice to promote fertilization and reproduction

Abstract

Summary 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.