@article{b4417b345ae04d848805ee79383e73f0,
title = "Stage-specific follicular extracellular vesicle uptake and regulation of bovine granulosa cell proliferation",
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.",
keywords = "Exosomes, Extracellular vesicles, Follicle, Follicular fluid, Granulosa cell, MAPK and PI3K, Proliferation, Src",
author = "Hung, {Wei Ting} and Raphatphorn Navakanitworakul and Tarique Khan and Pan Zhang and Davis, {John S.} and McGinnis, {Lynda K.} and Christenson, {Lane K.}",
note = "Funding Information: 1Department Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, USA; 2Department of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Hatyai, Songkhla, Thailand; 3Stowers Institute for Medical Research, Kansas City, Missouri, USA;4Department of Obstetrics and Gynecology, University of Nebraska Medical Center and VA Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA and 5Department Obstetrics and Gynecology, University of Southern California, Norris Cancer Center, Los Angeles, California, USA ∗Correspondence: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Blvd., Mail Stop 3043, Kansas City, KS 66160, USA. Tel: +913-588-0420; Fax: +913-588-7180; Email: lchristenson@kumc.edu †Grant Support: We also wish to acknowledge several core facilities that were essential for completion of this work: University of Kansas Medical Center Electron Microscopy Research Lab facility is supported in part, by NIH COBRE grant 9P20GM104936. The JEOL JEM-1400 TEM used in the study was purchased with funds from NIH grant S10RR027564.The work was funded by National Institute of Child Health and Human Development: HD061580 to LKC and HD082484 to LKC and LKM, Olson Center for Women{\textquoteright}s Health and Department of Veterans Affairs Office of Research and Development Biomedical Laboratory Research and Development funds to JSD. Funding Information: We also wish to acknowledge several core facilities that were essential for completion of this work: University of Kansas Medical Center Electron Microscopy Research Lab facility is supported in part, by NIH COBRE grant 9P20GM104936. The JEOL JEM-1400 TEM used in the study was purchased with funds from NIH grant S10RR027564.The work was funded by National Institute of Child Health and Human Development: HD061580 to LKC and HD082484 to LKC and LKM, Olson Center for Women's Health and Department of Veterans Affairs Office of Research and Development Biomedical Laboratory Research and Development funds to JSD. Publisher Copyright: {\textcopyright}The Authors 2017.",
year = "2017",
month = oct,
day = "1",
doi = "10.1093/biolre/iox106",
language = "English (US)",
volume = "97",
pages = "644--655",
journal = "Biology of Reproduction",
issn = "0006-3363",
publisher = "Society for the Study of Reproduction",
number = "4",
}