Transplantation of human umbilical cord-derived mesenchymal stem cells improves age-related ovarian functional decline via regulating the local renin–angiotensin system on inflammation and oxidative stress

作者：Lun Wei, Le Bo, Chao Luo, Na Yin, Wangtao Jiang, Fei Qian, Anwen Zhou, Xuanping Lu, Huiping Guo, Caiping Mao · 发表于：Stem Cell Research & Therapy · 年份：2024 · DOI：10.1186/s13287-024-03997-6 · 被引用次数：10 · 研究领域：Reproductive Biology and Fertility、Reproductive System and Pregnancy、Renin-Angiotensin System Studies

BACKGROUND: Age-related reproductive aging is a natural and irreversible physiological process, and delaying childbearing is increasingly common all over the world. Transplantation of mesenchymal stem cells (MSCs) is considered a new and effective therapy to restore ovarian function, but the relevant mechanisms remain unclear. Recently, it has been found that there is a local Renin-angiotensin system (RAS) in human ovary and it plays a key role. METHODS: After collecting follicular fluid from women who received oocyte retrieval for pure male factor infertility, the level of RAS components in it were detected, and the correlation analysis by linear regression. Then, the in vivo experiments on female C57BL/6 mice were designed to measure ovarian function, and the transcription and translation levels of RAS pathway were detected by molecular biology methods. Moreover, the role of RAS in regulating inflammation and oxidative stress in the co-culture system were explored in in vitro experiments on KGN cells. RESULTS: First, a total of 139 samples of analyzable follicular fluid were obtained. The local RAS of ovary, which is independent of systemic RAS (P > 0.05), is affected by age (Pearson r < 0, P < 0.05) and related to ovarian function, inflammation, oxidative stress indexes and assisted reproduction laboratory outcomes (P < 0.05). Next, the ovary/body weight of aging mice decreased significantly and serum sex hormones levels changed significantly (P < 0.01). The number of func...