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

Guan Yu Xiao; Chun Chun Cheng; Yih Shien Chiang; Winston Teng Kuei Cheng; I. Hsuan Liu; Shinn Chih Wu

doi:10.1038/srep23120

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

Guan Yu Xiao
, Chun Chun Cheng
, Yih Shien Chiang
, Winston Teng Kuei Cheng
, I. Hsuan Liu
, Shinn Chih Wu

Research output: Contribution to journal › Article › peer-review

188 Scopus citations

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.

Original language	English
Article number	23120
Journal	Scientific Reports
Volume	6
DOIs	https://doi.org/10.1038/srep23120
State	Published - Mar 16 2016

Bibliographical note

Funding 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.

Funding

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.

Funders	Funder number
Ministerio de Ciencia Tecnología y Telecomunicaciones	101-2313-B-002-017-MY3
Ministerio de Ciencia Tecnología y Telecomunicaciones

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10.1038/srep23120

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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.",

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note = "Funding 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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AU - Liu, I. Hsuan

AU - Wu, Shinn Chih

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PY - 2016/3/16

Y1 - 2016/3/16

N2 - 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.

AB - 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.

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

Abstract

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