2. Academic Validation
  3. Melatonin suppresses serum starvation-induced autophagy of ovarian granulosa cells in premature ovarian insufficiency

Melatonin suppresses serum starvation-induced autophagy of ovarian granulosa cells in premature ovarian insufficiency

  • BMC Womens Health. 2022 Nov 24;22(1):474. doi: 10.1186/s12905-022-02056-7.
Di Wu 1,  Wenjie Zhao 1,  Chengjuan Xu 2,  Xin Zhou 3,  Xia Leng 1,  Yanmin Li 4
Affiliations

Affiliations

  • 1 Department of Reproductive Medicine, Weifang People's Hospital, No.151 Guangwen Street, Kuiwen DistrictShandong Province, Weifang City, 261041, China.
  • 2 Department of Gynecology, Shouguang People's Hospital, Weifang, 262700, Shandong, China.
  • 3 Quality Management Office of Weifang People's Hospital, Weifang, 262700, China.
  • 4 Department of Reproductive Medicine, Weifang People's Hospital, No.151 Guangwen Street, Kuiwen DistrictShandong Province, Weifang City, 261041, China. [email protected].
PMID: 36434569 DOI: 10.1186/s12905-022-02056-7
Abstract

Objectives: Premature ovarian insufficiency (POI) refers to the decline and cessation of ovarian functions in women under 40 years of age. Melatonin (MT) acts as a protective for the ovary. This study elucidated the role of MT in Autophagy of granulosa cells (GCs) in POI via modulating the phosphatidylinositol-3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) pathway.

Methods: The expression levels of MicroRNA (miR)-15a-5p, signal transducer and activator of transcription 3 (STAT3), and relevant Hormones in the clinically collected serum samples of POI patients and healthy controls were examined. Human ovarian granulosa-like tumor cells (KGN) underwent serum starvation (SS) treatment to induce POI cell models and then received MT treatment. The expression levels of miR-15a-5p, STAT3, p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR in KGN cells were tested via quantitative real-time polymerase chain reaction and Western blotting. KGN cell viability was assessed by MTT assay and the protein levels of autophagy-related markers Beclin-1, microtubule-associated protein LIGHT chain 3 II/I, and p62 were detected by Western blotting. The binding relation between miR-15a-5p and STAT3 was verified via the dual-luciferase reporter gene assay. Functional rescue experiments were performed to probe the underlying role of miR-15a-5p/STAT3/the PI3K-Akt-mTOR pathway in KGN cell Autophagy.

Results: miR-15a-5p was increased whilst STAT3 was decreased in the serum of POI patients and SS-induced KGN cells. MT inhibited miR-15a-5p and STAT3, activated the PI3K-Akt-mTOR pathway, and repressed cell Autophagy in SS-induced KGN cells. miR-15a-5p targeted and repressed STAT3 expression. Upregulation of miR-15a-5p or downregulation of STAT3 or the PI3K-Akt-mTOR pathway promoted KGN cell Autophagy.

Conclusion: MT suppressed miR-15a-5p and activated STAT3 and the PI3K-Akt-mTOR pathway, finally impeding SS-induced Autophagy of GCs.

Keywords

Autophagy; Granulosa cells; Melatonin; PI3K-Akt-mTOR pathway; Premature ovarian insufficiency; Serum starvation; Stat3; miR-15a-5p.

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