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SESN2 Ameliorates Dihydrotestosterone-induced Human Ovarian Granulosa Cell Damage by Activating AMPK/ULK1-mediated

Xiaojing Hua1, Qing Lu1, Li Zeng2

  • 1Department of Gynecology, Affiliated Maternity and Child Health Care Hospital of Nantong University, Nantong City, Jiangsu Province, 226018, China.

Cell Biochemistry and Biophysics
|October 17, 2024
PubMed

Insights

Sestrin 2 (SESN2) protects against polycystic ovary syndrome (PCOS) by reducing granulosa cell apoptosis and oxidative stress. It achieves this by activating the AMPK/ULK1 pathway, which promotes mitophagy, counteracting dihydrotestosterone (DHT) effects.

Area of Science:

  • Reproductive Biology
  • Cellular Signaling
  • Molecular Mechanisms

Background:

  • Sestrin 2 (SESN2) regulates ovarian granulosa cell function, but its role in polycystic ovary syndrome (PCOS) remains unclear.
  • Dihydrotestosterone (DHT) is used to induce a PCOS cellular model in human granulosa-like cells (HGLS).

Purpose of the Study:

  • To investigate the functional role and underlying mechanism of SESN2 in DHT-induced granulosa cells.
  • To explore SESN2's impact on apoptosis, oxidative stress, and mitophagy in a PCOS model.

Main Methods:

  • DHT was used to establish a PCOS cell model; Compound C (CC) inhibited the AMP-activated protein kinase (AMPK) pathway.
  • Quantitative real-time PCR (qRT-PCR) and western blot analyzed protein and gene expression.
  • Flow cytometry and specific kits assessed cell apoptosis and oxidative stress markers.

Main Results:

  • SESN2 expression was downregulated in DHT-induced granulosa cells.
  • SESN2 overexpression mitigated DHT-induced apoptosis and oxidative stress in HGLS cells.
  • SESN2 activated the AMPK/ULK1 signaling pathway, promoting mitophagy, an effect reversed by CC.

Conclusions:

  • SESN2 plays a protective role in PCOS by suppressing DHT-induced apoptosis and oxidative stress.
  • The protective mechanism involves SESN2-mediated activation of the AMPK/ULK1 pathway, leading to enhanced mitophagy.
Keywords:
AMPK/ULK1Polycystic ovarian syndromeSestrin 2granulosa cellmitophagy

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