Stage-specific follicular extracellular vesicle uptake and regulation of bovine granulosa cell proliferation

Wei Ting Hung, Raphatphorn Navakanitworakul, Tarique Khan, Pan Zhang, John S. Davis, Lynda K. McGinnis, Lane K. Christenson

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)644-655
Number of pages12
JournalBiology of reproduction
Issue number4
StatePublished - Oct 1 2017


  • Exosomes
  • Extracellular vesicles
  • Follicle
  • Follicular fluid
  • Granulosa cell
  • MAPK and PI3K
  • Proliferation
  • Src

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology


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