Programming the oocyte's legacy

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This research program is exploring intergenerational programming through oocytes in the bovine species. For 3 decades, our laboratory has been involved in the understanding of the oocyte quality in bovine. Our recent discoveries indicate that the metabolic context perceived by the follicular cells surrounding the oocyte is a major determinant of the quality control process that ensures the production of a viable oocyte. We have also discovered that the information transmitted through the oocyte is not only important to produce a viable embryo but impacts the metabolic programming of the future individual. This epigenetic phenomenon is now emerging as a new paradigm in mammalian reproduction, and we have made substantial contribution to this field. We discovered that both mothers (cows) and fathers (bull) transmit information by the gametes to the embryos using non-genetic mechanisms (DNA methylation, micro-RNA and histones changes or retention). Our hypothesis is that the metabolic programming carried by the oocyte to the next generation relies on epigenetic mechanisms that are highly influenced by the follicular environment or in vitro culture conditions. To test this hypothesis, our first objective is to assess the impact of modulating energy metabolism modulators (lipids, sugars and metabolites) during in vitro maturation (IVM) of bovine oocytes and resulting blastocysts based on the post-partum cow's physiology. Considering the importance of the cumulus cells, our second objective is to investigate the acute response to metabolic stress in cumulus cells to understand how it may change the information and nutrients provided to the oocyte and then follow the oocyte to the blastocyst stage to assess the consequences of these modifications. In other words, we want to identify the molecular signature of metabolism-related epigenetic modifications that are transmitted across generations. We have also discovered that mitochondrial function is one of the major determinants of oocyte-embryo quality. Our results have shown that most metabolic stresses during late gametogenesis results in mitochondrial dysfunction in the day 7 embryo and poor quality. Therefore, our third objective is to modulate and monitor mitochondrial activity during IVM using activators of Beta-oxidation (e.g. L-carnitine), attenuation molecules (e.g. melatonin) or metabolic inhibitors to assess the effect on mitochondrial-gene expression and DNA methylation changes on the mitochondria genome. We postulate that the oocytes mitochondria are maintained in a `quiet' mode to prevent free radical formation until the blastocyst stage and that situation demands a specific metabolic programming which impacts both the embryo survival and the future metabolism of the F-1 generation. This research will certainly have an impact on how cow's oocytes and embryos are cultures to optimized their survival and the health of the offsprings.