title: Exosomal miR-10a derived from amniotic fluid stem cells preserves ovarian follicles after chemotherapy.
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.
authors.affiliation: Institute of Biotechnology, National Taiwan University, Taipei, Taiwan.
authors.forename: Guan-Yu
authors.initials: GY
authors.lastname: Xiao
authors.affiliation: The Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chun-Chun
authors.initials: CC
authors.lastname: Cheng
authors.affiliation: Technology Commons, College of Life Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Yih-Shien
authors.initials: YS
authors.lastname: Chiang
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan.|Department of Animal Science and Biotechnology, Tunghai University, Taichung, Taiwan.
authors.forename: Winston Teng-Kuei
authors.initials: WT
authors.lastname: Cheng
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan.|Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: I-Hsuan
authors.initials: IH
authors.lastname: Liu
authors.affiliation: Institute of Biotechnology, National Taiwan University, Taipei, Taiwan.|Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan.
authors.forename: Shinn-Chih
authors.initials: SC
authors.lastname: Wu
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects; D017209:Apoptosis; D001483:Base Sequence; D001665:Binding Sites; D002470:Cell Survival; D002478:Cells, Cultured; D018920:Coculture Techniques; D003520:Cyclophosphamide / Q000009:adverse effects; D055354:Exosomes / Q000378:metabolism; D005260:Female; D005496:Follicular Atresia / Q000187:drug effects; D055785:Gene Knockdown Techniques; D008813:Mice, Inbred ICR; D035683:MicroRNAs / Q000378:metabolism / Q000627:therapeutic use*; D006080:Ovarian Follicle / Q000187:drug effects / Q000502:physiology*; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced / Q000517:prevention & control*; D034622:RNA Interference; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D018906:Antineoplastic Agents, Alkylating; C569259:MIRN10 microRNA, mouse; D035683:MicroRNAs; C534190:Mirn146 microRNA, mouse; D003520:Cyclophosphamide