1. Academic Validation
  2. 4-vinylcyclohexene diepoxide induces premature ovarian insufficiency in rats by triggering the autophagy of granule cells through regulating miR-144

4-vinylcyclohexene diepoxide induces premature ovarian insufficiency in rats by triggering the autophagy of granule cells through regulating miR-144

  • J Reprod Immunol. 2023 Mar 5;157:103928. doi: 10.1016/j.jri.2023.103928.
Qun Zhou 1 Xin Jin 2 Jiaxi Wang 1 Huifang Li 3 Lijuan Yang 4 Weibo Wu 5 Wenjun Chen 6
Affiliations

Affiliations

  • 1 Department of Gynecology and Obstetrics, The First Affiliated Hospital of Zhejiang Chinese Medical University, China.
  • 2 Department of Massage, The First Affiliated Hospital of Zhejiang Chinese Medical University, China.
  • 3 Department of TCM Gynecology, Tongxiang Maternal and Child Health-Care Center, China.
  • 4 Department of Gynecology, First School of Clinical Medicine,Yunnan University of Chinese Medicine, China.
  • 5 First School of Clinical Medicine, Zhejiang Chinese Medical University, China.
  • 6 Department of Gynecology and Obstetrics, The First Affiliated Hospital of Zhejiang Chinese Medical University, China. Electronic address: [email protected].
Abstract

This research explored the pathological and molecular mechanisms of 4-vinylcyclohexene diepoxide (VCD)-induced POI model. QRT-PCR was exploited to detect miR-144 expression in the peripheral blood of POI patients. Rat and KGN cells were treated with VCD to construct POI rat or cell model, respectively. After miR-144 agomir or MK-2206 treatment, miR-144 level, follicle damage, Autophagy level and expressions of key pathway-related proteins in rats were detected, and cell viability and Autophagy in KGN cells were detected. MiR-144 was apparently down-regulated in the peripheral blood of POI patients. Decreased miR-144 was viewed in both the serum and ovary of rats, yet this trend was apparently reversed by miR-144 agomir. The increased concentration of Follicle-stimulating hormone (FSH) and Luteinizing hormone (LH), along with decreased concentration of E2 and AMH, was observed in the serum of model rats, which was conspicuously negated by control agomir or miR-144 agomir. Increased number of autophagosomes, up-regulated PTEN, and inactivated Akt/m-TOR pathway induced by VCD in ovary tissues were strikingly offset by miR-144 agomir. Results of cytotoxicity assay revealed that 2 mM VCD prominently repressed KGN cell viability. In vitro experiments confirmed that miR-144 interfered with the effect of VCD on Autophagy in KGN cells through the Akt/mTOR pathway. Taken together, VCD triggers Autophagy to induce POI after targeting the Akt pathway by inhibiting miR-144, it suggest that up-regulation the expression of miR-144 may have the potential to treat POI.

Keywords

4-vinylcyclohexene diepoxide; AKT/mTOR pathway; Autophagy; MiR-144; Premature ovarian insufficiency.

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