人脐带间充质干细胞来源的外泌体通过自噬激活修复雷洛昔芬诱导的子宫内膜基质细胞损伤

IF 2.8 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology Pub Date : 2025-07-11 DOI:10.1016/j.reprotox.2025.108997

Shiling Chen , Xiuying Lin , Lei Liu , Jianhua Fu , Xiaodan Lu , Chunxue Niu , Qilai Wang , HaiFeng Wei , Mengxue Wu , Munan Sun , Lixin Cao , Xuguang Mi , Yanqiu Fang

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引用次数: 0

摘要

雌激素在月经周期中促进子宫内膜增厚起着核心作用。在子宫内膜薄的患者中，子宫内膜细胞对雌激素的敏感性降低，导致女性不孕。我们使用雌激素拮抗剂雷洛昔芬（raloxifene， RAL）建立了子宫内膜基质细胞损伤模型，并研究了人脐带间充质干细胞来源的外泌体（hUCMSC-EXO）在修复雌激素诱导的人子宫内膜基质细胞（hEndoSCs）损伤中的作用和潜在机制。在这项研究中，用RAL处理hEndoSCs，随后用hUCMSC-EXO培养。结果表明，hUCMSC-EXO恢复了hEndoSCs的增殖能力，减少了内源性活性氧的产生，增加了线粒体膜电位。机制分析表明，hUCMSC-EXO激活细胞内自噬，自噬抑制逆转了hUCMSC-EXO对hEndoSCs的保护作用。这些发现表明，hUCMSC-EXO可能改善与雌激素不敏感相关的子宫内膜损伤。

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

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.

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来源期刊

Reproductive toxicology 生物-毒理学

CiteScore

6.50

自引率

3.00%

发文量

131

审稿时长

45 days

期刊介绍： Drawing from a large number of disciplines, Reproductive Toxicology publishes timely, original research on the influence of chemical and physical agents on reproduction. Written by and for obstetricians, pediatricians, embryologists, teratologists, geneticists, toxicologists, andrologists, and others interested in detecting potential reproductive hazards, the journal is a forum for communication among researchers and practitioners. Articles focus on the application of in vitro, animal and clinical research to the practice of clinical medicine. All aspects of reproduction are within the scope of Reproductive Toxicology, including the formation and maturation of male and female gametes, sexual function, the events surrounding the fusion of gametes and the development of the fertilized ovum, nourishment and transport of the conceptus within the genital tract, implantation, embryogenesis, intrauterine growth, placentation and placental function, parturition, lactation and neonatal survival. Adverse reproductive effects in males will be considered as significant as adverse effects occurring in females. To provide a balanced presentation of approaches, equal emphasis will be given to clinical and animal or in vitro work. Typical end points that will be studied by contributors include infertility, sexual dysfunction, spontaneous abortion, malformations, abnormal histogenesis, stillbirth, intrauterine growth retardation, prematurity, behavioral abnormalities, and perinatal mortality.