文献类型：期刊文献

英文题名：Ovarian microenvironment remodeling in premature ovarian insufficiency: From hormone replacement to regenerative strategies with mesenchymal stem cells and exosomes

作者：Feng, Mingxia[1];Su, Jiamin[1];Yu, Guangjiao[1];Wu, Juanling[1];Li, Ying[1];Yang, Li[1];Liang, Tongtong[1];Yu, Lei[2];Zeng, Zhaoyang[3];Zhao, Fenqin[1]

第一作者：冯明霞

通信作者：Zhao, FQ[1]

机构：[1]Gansu Univ Chinese Med, Dept Obstet & Gynecol, 35 Dingxi East Rd, Lanzhou 730000, Gansu, Peoples R China;[2]Lanzhou Maternal & Child Hlth Care Hosp, Dept Obstet & Gynecol, Lanzhou, Gansu, Peoples R China;[3]Gansu Univ Chinese Med, Dept Surg, Lanzhou 730000, Gansu, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Dept Obstet & Gynecol, 35 Dingxi East Rd, Lanzhou 730000, Gansu, Peoples R China.|[10735]甘肃中医药大学;

年份：2026

卷号：177

外文期刊名：JOURNAL OF REPRODUCTIVE IMMUNOLOGY

收录：;Scopus(收录号：2-s2.0-105048819549);WOS:【SCI-EXPANDED(收录号:WOS:001865236600001)】；

基金：This work was supported by the National Natural Science Foundation of China (Nos. 82360877, 81760806) and the Natural Science Foundation of Gansu Province (No. 24JRRA1027) .

语种：英文

外文关键词：Premature ovarian insufficiency; Ovarian microenvironment; Hormone replacement therapy; Mesenchymal stem cells; SEVs; Regenerative medicine; Mitochondrial dysfunction

摘要：Premature ovarian insufficiency (POI) is a heterogeneous disorder characterized by loss of ovarian function before age 40, causing infertility, hypoestrogenism-related complications, and significantly impaired quality of life. Although hormone replacement therapy (HRT) remains the standard treatment for symptom relief and longterm health protection, it cannot restore ovarian reserve or natural fertility. This review summarizes the etiology and pathogenesis of POI, emphasizing mitochondrial dysfunction, oxidative stress, chronic inflammation, and progressive deterioration of the ovarian microenvironment. We critically evaluate the strengths and limitations of conventional HRT based on the latest 2024 international evidence-based guidelines, and comprehensively overview emerging regenerative therapies, focusing on mesenchymal stem cells (MSCs) and MSC-derived small extracellular vesicles (sEVs). MSCs exert therapeutic effects mainly through paracrine actions, including antiapoptotic, anti-inflammatory, and pro-angiogenic activities. MSC-sEVs, particularly hypoxia-preconditioned ones, offer a safer cell-free alternative. They protect mitochondrial function via the SIRT3/PGC-1 alpha pathway and other related mechanisms such as Nrf2/Keap1 and AMPK signaling. Current clinical evidence for both approaches remains preliminary, consisting mainly of small-scale trials with heterogeneous protocols and short follow-up. We propose an innovative ovarian microenvironment remodeling framework that integrates symptomatic HRT with etiology-targeted regenerative interventions using MSCs or engineered sEVs. In summary, while HRT forms the foundation of POI management, MSC-sEVs represent a highly promising cell-free platform that may shift the paradigm from hormone replacement to functional regeneration, restoring both endocrine function and fertility in POI patients.