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  

Placental mesenchymal stem cell exosome-derived miR-139-5p regulates PTEN gene and influences chemotherapeutic-induced ovarian dysfunction

作　　者：白雪峰 王少为[1] Bai Xuefeng;Wang Shaowei(Department of Gynecology and Obstetrics,Beijing Hospital,National Center of Gerontology,Beijing 100730,China)

机构地区：[1]北京医院妇产科国家老年医学中心,北京100730

出　　处：《中华妇产科杂志》2024年第9期710-718,共9页Chinese Journal of Obstetrics and Gynecology

基　　金：中央高水平医院临床科研业务费资助项目(BJ-2021-236)。

摘　　要：目的探讨胎盘间充质干细胞来源的外泌体及微小RNA(miRNA)对化疗损伤的卵巢颗粒细胞的影响。方法在多个公开数据库中检索靶向调控第10号染色体同源丢失性磷酸酶-张力蛋白基因(PTEN)的miRNA,确定目标miRNA。向人卵巢颗粒细胞中转染该目标miRNA后,检测细胞增殖及目标miRNA、PTEN表达情况。使用顺铂诱导人卵巢颗粒细胞的损伤,并与人胎盘间充质干细胞及其来源的外泌体共培养,检测细胞凋亡情况和PTEN、目标miRNA的表达。结果通过检索各数据库,最终选择miRNA 139-5p(miR-139-5p)作为本研究的目标miRNA。向人卵巢颗粒细胞中转染miR-139-5p的模拟物后,miR-139-5p的表达水平升高(9882.080±1049.130),PTEN蛋白的表达水平降低(0.78±0.11),细胞增殖吸光度增加(0.85±0.07)。使用顺铂处理后,人卵巢颗粒细胞发生明显损伤,凋亡增强,顺铂处理细胞的凋亡率高于未用顺铂处理者[分别为(41.9±1.0)%、(5.0±0.3)%,P<0.001]。在与人胎盘间充质干细胞及其来源的外泌体进行共培养后,损伤的人卵巢颗粒细胞的miR-139-5p表达水平升高(分别为1.31±0.04、1.20±0.03),凋亡减弱[细胞凋亡率分别为(20.0±0.4)%、(22.3±1.1)%]。结论胎盘间充质干细胞来源的外泌体对于由顺铂引起的卵巢颗粒细胞损伤有修复作用,可通过其包含的miR-139-5p靶向调控PTEN基因,miR-139-5p可能是治疗化疗性卵巢功能损伤的潜在靶点。ObjectiveTo investigate the impact of exosomes and microRNA(miRNA)from placental mesenchymal stem cells on chemotherapy-damaged ovarian granulosa cells.MethodsVarious 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.ResultsAfter 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(9882.080±1049.130),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].ConclusionPlacental 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.

关 键 词：原发性卵巢功能不全 间充质干细胞 外泌体 微RNAS PTEN磷酸水解酶 卵巢早衰 

分 类 号：R711.75[医药卫生—妇产科学]