Exosomal miR-10a derived from amniotic fluid stem cells preserves ovarian follicles after chemotherapy
Journal
Scientific Reports
Journal Volume
6
Date Issued
2016
Author(s)
Xiao, Guan-Yu
Cheng, Chun-Chun
Chiang, Yih-Shien
Cheng, Winston Teng-Kuei
Liu, I-Hsuan
Abstract
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.
SDGs
Other Subjects
alkylating agent; cyclophosphamide; microRNA; MIRN10 microRNA, mouse; Mirn146 microRNA, mouse; amnion fluid; animal; apoptosis; binding site; cell culture; cell survival; chemically induced; coculture; cytology; drug effects; exosome; female; gene silencing; Institute for Cancer Research mouse; nucleotide sequence; ovary follicle; ovary follicle atresia; physiology; Primary Ovarian Insufficiency; RNA interference; secretion (process); stem cell; stem cell transplantation; Amniotic Fluid; Animals; Antineoplastic Agents, Alkylating; Apoptosis; Base Sequence; Binding Sites; Cell Survival; Cells, Cultured; Coculture Techniques; Cyclophosphamide; Exosomes; Female; Follicular Atresia; Gene Knockdown Techniques; Mice, Inbred ICR; MicroRNAs; Ovarian Follicle; Primary Ovarian Insufficiency; RNA Interference; Stem Cell Transplantation; Stem Cells
Type
journal article