Exosomes derived from oviduct cells mediate the EGFR/MAPK signaling pathway in cumulus cells

Current studies indicate that application of oviduct cells (OCs) in in vitro system create microenvironment similar to the in vivo conditions by releasing multiple growth factors which has beneficial effects on the development of cumulus-oocyte complexes and embryos. In particular, recent evidence with a coculture system indicates that there is a reciprocal relationship between canine OCs and cumulus cells and that oviductal secretions can promote changes in cellular protein/gene expression. Despite the fact that OCs respond to cumulus cells, a clear understanding of the mechanism by which the components released from OCs that play a role in modulating the biological function of cumulus cells is still elusive. Therefore, we hypothesized that exosomes derived from OCs (OC-Exo), which efficiently mediate cellular communication by transferring their molecular cargo to recipient cells, could be key modulators of the cross-talk with cumulus cells. We aimed to characterize OC-Exo and decipher their physiological effects on cumulus cells via the epidermal growth factor receptor/mitogen-activated protein kinase (EGFR/MAPK) pathway, which is one of the prerequisite pathways for cell development. Exposure of OC-Exo improved physiological cumulus cell condition including cell concentration, viability, and proliferation rate could reduce the accumulation of reactive oxygen species and the apoptotic rate. Moreover, exosomes could enhance the messenger RNA transcript and protein levels related to EGFR signaling in cumulus cells. The present study provides the first evidence that OC-Exo effectively enhance the physiological condition of cumulus cells exposed to GW4869 or Gefitinib via the EGFR/MAPK signaling pathway and this could be the primary mediators of molecular interactions among cumulus cells and shedding light on the role of exosomes in cumulus cells might permit improvement of oocyte and embryo development in vitro.