Exosomal miR-10a derived from amniotic fluid stem cells preserves ovarian follicles after chemotherapy.
Exosomal miR-10a derived from amniotic fluid stem cells preserves ovarian follicles after chemotherapy.
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DOI：
10.1038/srep23120
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发表时间：
2016-03-16
影响因子：
4.6
通讯作者：
Wu SC
中科院分区：
文献类型：
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作者：
Xiao GY;Cheng CC;Chiang YS;Cheng WT;Liu IH;Wu SC
化疗（CTx）引起的卵巢早衰（POF）在临床上是不可逆的。羊水干细胞（AFSC）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。在这里，我们证明了AFSC衍生的外泌体概括了AFSC对CTX损伤的颗粒细胞（GC）的抗凋亡作用，这对卵泡的生长至关重要。AFSC衍生的外泌体通过递送microRNA预防CTX处理的小鼠中的卵巢卵泡闭锁，其中miR-146 a和miR-10 a高度富集，并且其潜在靶基因对细胞凋亡至关重要。这两种miRNA在AFSC衍生的外泌体中的下调减弱了体外对CTX损伤的GC的抗凋亡作用。此外，这些miRNA的施用概括了体外和体内的作用，其中miR-10a贡献了主导影响。我们的研究结果表明，miR-10a有潜力作为一种新的治疗药物治疗POF。
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.