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

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...

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Detalles Bibliográficos
Autores: Liu, Yan, Zhu, Xiaohe, Wu, Chunli, Lang, Yan, Zhao, Wenjie, Li, Yanmin
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:Brasil
Institución:Universidade de São Paulo (USP)
Repositorio:Clinics
Idioma:inglés
OAI Identifier:oai:revistas.usp.br:article/213568
Acceso en línea:https://www.revistas.usp.br/clinics/article/view/213568
Access Level:acceso abierto
Palabra clave:Autophagy
Effect
Melatonin
Ovarian Granulosa Cells
Ovarian damage
Descripción
Sumario: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.