Biased signaling pathways in cumulus-oocyte complexes

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During the last decades while milk production is increasing, fertility of the dairy cattle herd is decreasing. The utilization of in vitro culture system is one way to rapidly counter the decline of fertility. An important need of fundamental research is crucial for dairy cow industry that is one of the most important agri-food sectors in Canada, with a total farms receipts of $5.9 billion, 79 million hectolitres produced by 1.4 million of heads in 2012. *The proposed research program will study intracellular signaling mechanisms involved in oocyte meiotic resumption during in vitro maturation. Oocyte meiotic resumption is an essential event allowing the egg to be fertilized. The optimal window to improve oocyte quality occurs before oocyte meiotic resumption. Cumulus cells are the known modulators of oocyte developmental competence. The improvement of culture conditions, such as prolongation of the window by inhibiting oocyte meiotic resumption requires a better understanding of the signalling pathways involved.*It is well-known that cyclic adenosine monophosphate (cAMP) is a crucial second messenger in response of follicular cells to FSH (follicle-stimulating hormone). Cyclic AMP is a key regulator of oocyte meiotic resumption in mammals. The resultant of synthesis and degradation modulates intracellular cAMP concentration. Beyond cAMP synthesis, the degradation by phosphodiesterases (PDE) is a powerful modulator inducing physiological response of the cells. It is thus that caffeine, a non-specific PDE inhibitor, is part of our daily life with a cup of coffee. The most spectacular example relies on Viagrar a specific PDE inhibitor prescribed for almost two decades in men with erectile dysfunction. These examples are illustrating how PDE may impact the daily life by affecting crucial mammalian physiological events. *Over the last years my laboratory has been interested in understanding the role of PDE in different reproductive functions. Although PDE3A is functionally present in bovine oocytes, one of our recent findings is that PDE8 was present in bovine oocyte and cumulus cells. Our working hypothesis is stating that cAMP degradation by PDE8 plays a physiological role in ovarian follicular cells signaling as part of an integrative signaling cellular response. We will thus investigate the role of PDE8 in bovine cumulus-oocytes complexes during in vitro maturation. This will be analyzed in response to induction of in vitro oocyte meiotic resumption by FSH and epidermal growth factor, and in response to inhibition by C-type natriuretic peptide. *The improvement of oocyte quality will be achieved through a better understanding of the signalling events occurring prior to oocyte meiotic resumption during the first hours of in vitro maturation. Because the improvement of in vitro embryo production is a matter of urgency for embryo transfer companies, this project would reveal the knowledge required to enable progress in the development of diagnostic and therapeutic tools. Such advances are of prime importance to the dairy cow industry because of the observed decreases in dairy herd fertility. This program will assess fundamental signalling and thus provide immediate beneficial applications in the short-term.