Melatonin protects against ovarian damage by inhibiting autophagy in granulosa cells in rats

Authors

  • Yan Liu Weifang People's Hospital
  • Xiaohe Zhu Weifang People's Hospital
  • Chunli Wu Weifang People's Hospital
  • Yan Lang Weifang People's Hospital
  • Wenjie Zhao Weifang People's Hospital
  • Yanmin Li Weifang People's Hospital https://orcid.org/0000-0002-2478-5485

DOI:

https://doi.org/10.1016/j.clinsp.2022.100119

Keywords:

Autophagy, Effect, Melatonin, Ovarian Granulosa Cells, Ovarian damage

Abstract

Objectives: This study sought to further verify the protective mechanism of Melatonin (MT) against ovarian damage through animal model experiments and to lay a theoretical and experimental foundation for exploring new approaches for ovarian damage treatment.

Method: The wet weight and ovarian index of rat ovaries were weighted, and the morphology of ovarian tissues and the number of follicles in the pathological sections of collected ovarian tissues were recorded. And the serum sex hormone levels, the key proteins of the autophagy pathway (PI3K, AKT, mTOR, LC3II, LC3I, and Agt5) in rat ovarian tissues, as well as the viability and mortality of ovarian granulosa cells in each group were measured by ELISA, western blotting, CCK8 kit and LDH kit, respectively.

Results: The results showed that MT increased ovarian weight and improved the ovarian index in ovarian damage rats. Also, MT could improve autophagy-induced ovarian tissue injury, increase the number of primordial follicles, primary follicles, and sinus follicles, and decrease the number of atretic follicles. Furthermore, MT upregulated serum AMH, INH-B, and E2 levels downregulated serum FSH and LH levels in ovarian damage rats and activated the PI3K/AKT/mTOR signaling pathway. Besides, MT inhibited autophagic apoptosis of ovarian granulosa cells and repressed the expression of key proteins in the autophagic pathway and reduced the expression levels of Agt5 and LC3II/I.

Conclusions: MT inhibits granulosa cell autophagy by activating the PI3K/Akt/mTOR signaling pathway, thereby exerting a protective effect against ovarian damage.

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Published

2022-10-01

Issue

Section

Original Articles

How to Cite

Liu, Y., Zhu, X., Wu, C., Lang, Y., Zhao, W., & Li, Y. (2022). Melatonin protects against ovarian damage by inhibiting autophagy in granulosa cells in rats. Clinics, 77, 100119. https://doi.org/10.1016/j.clinsp.2022.100119