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

Toxicology and Cancer Biology

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

134 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.

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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.",

author = "Xiao, {Guan Yu} and Cheng, {Chun Chun} and Chiang, {Yih Shien} and Cheng, {Winston Teng Kuei} and Liu, {I. Hsuan} and Wu, {Shinn Chih}",

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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doi = "10.1038/srep23120",

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AU - Xiao, Guan Yu

AU - Cheng, Chun Chun

AU - Chiang, Yih Shien

AU - Cheng, Winston Teng Kuei

AU - Liu, I. Hsuan

AU - Wu, Shinn Chih

N1 - 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.

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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