Human umbilical cord mesenchymal stem cell-derived exosomes repair raloxifene-induced damage in endometrial stromal cells via autophagy activation

  • Reprod Toxicol. 2025 Jul 11:137:108997. doi: 10.1016/j.reprotox.2025.108997.
Shiling Chen  1 ,  Xiuying Lin  2 ,  Lei Liu  2 ,  Jianhua Fu  2 ,  Xiaodan Lu  3 ,  Chunxue Niu  1 ,  Qilai Wang  1 ,  HaiFeng Wei  1 ,  Mengxue Wu  2 ,  Munan Sun  2 ,  Lixin Cao  1 ,  Xuguang Mi  4 ,  Yanqiu Fang  5
Affiliations
  • 1. Central laboratory, Jilin Province People's Hospital, Changchun, China.
  • 2. Reproductive Medicine Center, Jilin Province People's Hospital, Changchun, China.
  • 3. Precision Molecular Medicine Center, Jilin Province People's Hospital, Changchun, China.
  • 4. Central laboratory, Jilin Province People's Hospital, Changchun, China. Electronic address: [email protected].
  • 5. Reproductive Medicine Center, Jilin Province People's Hospital, Changchun, China. Electronic address: [email protected].
PMID: 40652993 DOI: 10.1016/j.reprotox.2025.108997
Abstract

Estrogen plays a central role in promoting endometrial thickening during the menstrual cycle. In patients with a thin endometrium, endometrial cells exhibit reduced sensitivity to estrogen, contributing to female infertility. We established an endometrial stromal cell damage model using the estrogen antagonist raloxifene (RAL) and investigated the role and underlying mechanism of human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-EXO) in repairing RAL-induced damage in human endometrial stromal cells (hEndoSCs). In this study, hEndoSCs were treated with RAL and subsequently cultured with hUCMSC-EXO. The results showed that hUCMSC-EXO restored the proliferative capacity of hEndoSCs, decreased endogenous Reactive Oxygen Species production, and increased mitochondrial membrane potential. Mechanistic analysis indicated that hUCMSC-EXO activated intracellular Autophagy, and that Autophagy inhibition reversed the protective effects of hUCMSC-EXO on hEndoSCs. These findings suggest that hUCMSC-EXO may ameliorate endometrial injury associated with estrogen insensitivity.

Keywords
Autophagy; HEndoSCs; HUCMSC-EXO; Raloxifene.
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