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Obeticholic acid treatment of mice to promote fertilization and reproduction

Published online by Cambridge University Press:  01 September 2023

Ming Liang ,
Huailiang Yang ,
Lanyong Xu  and
Longqiao Cao Open the ORCID record for Longqiao Cao [Opens in a new window]
Ming Liang
Affiliation:
Department of Reproductive Medicine, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250001, Shandong Province, China
Huailiang Yang
Affiliation:
Department of Reproductive Medicine, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250001, Shandong Province, China
Lanyong Xu
Affiliation:
The People’s Hospital of Gaotang, Gaotang People’s Hospital Affiliated to Jining Medical College, Gaotang, 252800, Shandong Province, China
Longqiao Cao*
Affiliation:
Department of Reproductive Medicine, The First People’s Hospital of Jining, Jining, 272011, Shandong Province, China
*
Corresponding author: Longqiao Cao; Email: caolongqiang2023@163.com
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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.

Keywords

Mitochondrial activityObeticholic acidOxidative stressReproduction
Type
Research Article
Information
Zygote , Volume 31 , Issue 6 , December 2023 , pp. 527 - 536
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Copyright
© The Author(s), 2023. Published by Cambridge University Press

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