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28 August 2017 Stage-specific follicular extracellular vesicle uptake and regulation of bovine granulosa cell proliferation
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Abstract

Follicular fluid within ovarian antral follicles contains numerous factors, which influence the development of a healthy oocyte including nucleic acids, steroids, proteins, and extracellular vesicles (EVs). Current evidence indicates that follicular EVs promote changes in cellular gene expression and support cumulus–oocyte complex expansion in vitro. In this study, we found EVs from different sized follicles differentially stimulate granulosa cell proliferation and this could be explained by both the differential contents associated, on or within the vesicles and by the preferential uptake of EVs dependent on follicle size from which they were isolated. Antibody array and inhibitor studies indicated that the Src, PI3K/Akt, and MAPK signaling pathways mediate the stimulatory effects of EVs on granulosa cell proliferation. This study demonstrates for the first time that EVs isolated from follicular fluid are capable of stimulating granulosa cell proliferation and that this stimulatory response is associated with the size of antral follicle from which the EVs originated. The study further also provides the first evidence that vesicles released by small antral follicles are preferentially taken up when compared to those isolated from large follicles, suggesting that vesicular surface proteins change during follicular maturation.

Summary Sentence

Follicular fluid derived extracellular vesicles exhibit differential ability to stimulate granulosa cell proliferation and uptake that is dependent upon the stage of follicle development.

© The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Wei-Ting Hung, Raphatphorn Navakanitworakul, Tarique Khan, Pan Zhang, John S. Davis, Lynda K. McGinnis, and Lane K. Christenson "Stage-specific follicular extracellular vesicle uptake and regulation of bovine granulosa cell proliferation ," Biology of Reproduction 97(4), 644-655, (28 August 2017). https://doi.org/10.1093/biolre/iox106
Received: 28 February 2017; Accepted: 25 August 2017; Published: 28 August 2017
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