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.
|State||Published - Mar 16 2016|
Bibliographical noteFunding Information:
We thank Joint Center for Instruments and Researches at College of Bioresources and Agriculture at National Taiwan University for technical support in fluorescence microscope; Technology Commons in College of Life Science and Center for Systems Biology at National Taiwan University for experiments in transmission electron microscopy and NGS and data analysis; Ju-Ting Cheng for drawing the figure 4c. This work was supported by Ministry of Science and Technology grant 101-2313-B-002-017-MY3.
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