Xiao Guan-Yu, Cheng Chun-Chun, Chiang Yih-Shien, Cheng Winston Teng-Kuei, Liu I-Hsuan, Wu Shinn-Chih
Institute of Biotechnology, National Taiwan University, Taipei, Taiwan.
The Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
Sci Rep. 2016 Mar 16;6:23120. doi: 10.1038/srep23120.
Chemotherapy (CTx)-induced premature ovarian failure (POF) in woman remains clinically irreversible. Amniotic fluid stem cells (AFSCs) have shown the potential to treat CTx-induced POF; however, the underlying mechanism is unclear. Here we demonstrate that AFSC-derived exosomes recapitulate the anti-apoptotic effect of AFSCs on CTx-damaged granulosa cells (GCs), which are vital for the growth of ovarian follicles. AFSC-derived exosomes prevent ovarian follicular atresia in CTx-treated mice via the delivery of microRNAs in which both miR-146a and miR-10a are highly enriched and their potential target genes are critical to apoptosis. The down-regulation of these two miRNAs in AFSC-derived exosomes attenuates the anti-apoptotic effect on CTx-damaged GCs in vitro. Further, the administration of these miRNAs recapitulates the effects both in vitro and in vivo, in which miR-10a contributes a dominant influence. Our findings illustrate that miR-10a has potential as a novel therapeutic agent for the treatment of POF.
化疗(CTx)诱导的女性卵巢早衰(POF)在临床上仍然不可逆转。羊水干细胞(AFSCs)已显示出治疗CTx诱导的POF的潜力;然而,其潜在机制尚不清楚。在此我们证明,AFSC衍生的外泌体重现了AFSCs对CTx损伤的颗粒细胞(GCs)的抗凋亡作用,而颗粒细胞对卵泡生长至关重要。AFSC衍生的外泌体通过递送微小RNA来预防CTx处理小鼠的卵巢卵泡闭锁,其中miR-146a和miR-10a高度富集,且它们的潜在靶基因对细胞凋亡至关重要。AFSC衍生外泌体中这两种微小RNA的下调减弱了对体外CTx损伤的GCs的抗凋亡作用。此外,这些微小RNA的给药在体外和体内均重现了其作用,其中miR-10a起主要作用。我们的研究结果表明,miR-10a有潜力作为治疗POF的新型治疗剂。
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