hUCMSC-derived extracellular vesicles relieve cisplatin-induced granulosa cell apoptosis in mice by transferring antiapoptotic miRNAs  

作　　者：Wenjing Tang Haiyan Yan Xiaojun Chen Yanan Pu Xin Qi Liyang Dong Chuan Su 

机构地区：[1]State Key Laboratory of Reproductive Medicine and Offspring Health,Nanjing Medical University,Nanjing,Jiangsu 211166,China [2]Department of Pathogen Biology&Immunology,Nanjing Medical University,Nanjing,Jiangsu 211166,China [3]Department of Nuclear Medicine,the Affiliated Hospital of Jiangsu University,Zhenjiang,Jiangsu 212000,China

出　　处：《Journal of Biomedical Research》2025年第1期36-49,共14页生物医学研究杂志(英文版)

基　　金：Financial support for the current study was provided by the grant from"Blue Engineering"Excellent Young Teacher Foundation in Colleges and Universities of Jiangsu Province(Grant No.KY101R202207 to Xiaojun Chen)。

摘　　要：Premature ovarian insufficiency(POI)caused by chemotherapy is a common complication in female cancer survivors of childbearing age.Traditional methods,including mesenchymal stem cell(MSC)transplant and hormone replacement therapy,have limited clinical application because of their drawbacks,and more methods need to be developed.In the current study,the potential effects and underlying mechanisms of human umbilical cord MSC-derived extracellular vesicles(h UCMSC-EVs)were investigated in a cisplatin(CDDP)-induced POI mouse model and a human granulosa cell(GC)line.The results showed that h UCMSC-EVs significantly attenuated body weight loss,ovarian weight loss,ovary atrophy,and follicle loss in moderate-dose(1.5 mg/kg)CDDP-induced POI mice,similar to the effects observed with h UCMSCs.We further found that the h UCMSCEVs inhibited CDDP-induced ovarian GC apoptosis by upregulating anti-apoptotic mi RNA levels in GCs,thereby downregulating the m RNA levels of multiple pro-apoptotic genes.In general,our findings indicate that the moderate-dose chemotherapy may be a better choice for clinical oncotherapy,considering effective rescue of the oncotherapy-induced ovarian damage with h UCMSC-EVs.Additionally,multiple mi RNAs in h UCMSC-EVs may potentially be used to inhibit the chemotherapy-induced ovarian GC apoptosis,thereby restoring ovarian function and improving the life quality of female cancer patients.

关 键 词：CHEMOTHERAPY fertility preservation extracellular vesicles granulosa cell apoptosis microRNAs 

分 类 号：R711.75[医药卫生—妇产科学]