Placental mesenchymal stem cell exosome-derived miR-139-5p regulates PTEN gene and influences chemotherapeutic-induced ovarian dysfunction
10.3760/cma.j.cn112141-20240419-00228
- VernacularTitle:胎盘间充质干细胞来源的外泌体中miR-139-5p调控PTEN基因影响化疗性卵巢功能损伤的研究
- Author:
Xuefeng BAI
1
;
Shaowei WANG
Author Information
1. 北京医院妇产科 国家老年医学中心，北京 100730
- Keywords:
Premature ovarian insufficiency;
Mesenchymal stem cells;
Exosomes;
MicroRNAs;
PTEN phosphohydrolase;
Premature ovarian failure
- From:
Chinese Journal of Obstetrics and Gynecology
2024;59(9):710-718
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the impact of exosomes and microRNA (miRNA) from placental mesenchymal stem cells on chemotherapy-damaged ovarian granulosa cells.Methods:Various public databases were searched for miRNA targeting phosphatase and tensin homologue deleted on chromosome 10 (PTEN) gene. After miRNA transfection into human ovarian granulosa cells, cell growth and expressions of the target miRNA and PTEN were detected. Cisplatin was utilized to induce damage to human ovarian granulosa cells, which were subsequently co-cultured with human placental mesenchymal stem cells and exosomes generated from mesenchymal stem cells, then apoptosis and expressions of PTEN and the target miRNA were detected.Results:After analyzing several databases, miRNA 139-5p (miR-139-5p) was chosen as the target miRNA for this research. Transfection of miR-139-5p mimics into human ovarian granulosa cells elevated miR-139-5p expression level (9 882.080±1 049.130), reduced PTEN protein expression level (0.78±0.11), and increased cell proliferation absorbance (0.85±0.07). Cisplatin treatment severely damaged human ovarian granulosa cells and increased apoptosis, cisplatin-treated cells had a higher apoptosis ratio compared to untreated cells [ (41.9±1.0)% vs (5.0±0.3)%, P<0.001]. In damaged human ovarian granulosa cells, co-cultured with human placental mesenchymal stem cells and exosomes increased miR-139-5p expression levels (1.31±0.04 and 1.20±0.03, respectively) and decreased apoptosis ratios [(20.0±0.4)% and (22.3±1.1)%, respectively]. Conclusion:Placental mesenchymal stem cell-derived exosomes repair damages of cisplatin-induced ovarian granulosa cell and could target PTEN gene through miR-139-5p, which might be a potential option for the treatment of chemotherapy-induced ovarian dysfunction.
