Exosomal miR-10a derived from amniotic fluid stem cells preserves ovarian follicles after chemotherapy

Sci Rep. 2016 Mar 16:6:23120. doi: 10.1038/srep23120.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amniotic Fluid / cytology
  • Animals
  • Antineoplastic Agents, Alkylating / adverse effects
  • Apoptosis
  • Base Sequence
  • Binding Sites
  • Cell Survival
  • Cells, Cultured
  • Coculture Techniques
  • Cyclophosphamide / adverse effects
  • Exosomes / metabolism
  • Female
  • Follicular Atresia / drug effects
  • Gene Knockdown Techniques
  • Mice, Inbred ICR
  • MicroRNAs / metabolism
  • MicroRNAs / therapeutic use*
  • Ovarian Follicle / drug effects
  • Ovarian Follicle / physiology*
  • Primary Ovarian Insufficiency / chemically induced
  • Primary Ovarian Insufficiency / prevention & control*
  • RNA Interference
  • Stem Cell Transplantation
  • Stem Cells / metabolism*

Substances

  • Antineoplastic Agents, Alkylating
  • MIRN10 microRNA, mouse
  • MicroRNAs
  • Mirn146 microRNA, mouse
  • Cyclophosphamide