Mechanisms affecting oocyte competence in the bovine model: effect of follicular and maternal aging

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The most critical period influencing the success or failure of pregnancy is the first 7 days. More than 95% of oocytes (eggs) become fertilized after insemination (conception) but only 10-40% of them produce embryos. The reason for this high rate of attrition during early embryonic development is unclear, but is associated with the intrinsic status of the oocyte. The long-term objective of this research program is to elucidate the hormonal, cellular and molecular mechanisms that affect an oocyte's ability to develop into a viable embryo. This application is a logical extension of fruitful line of research established with NSERC funding. We developed the bovine model for the study of reproductive aging and documented that maternal aging in the bovine model is associated with a decrease in oocyte competence. Our recent results suggest that oocyte competence is also compromised when the life-span of a growing follicle is prolonged by even 3-4 days. In this grant, we want to address the fundamental biological question: How does oocyte dysfunction occur in vivo? Therefore, the focus of the proposed research is to understand the mechanisms associated with loss of oocyte competence during follicular and maternal aging. Our overall working hypothesis is that the loss of oocyte competence is caused by similar cytoplasmic events during maternal and follicular aging while chromosomal dysfunctions are unique to maternal aging. The specific objectives of this grant are, to determine 1) the precise embryonic stage/event affected by follicular and maternal aging, 2) the role of chromosomal non-disjunctions and spindle defects during loss of oocyte competence, 3) if telomere shortening of oocyte chromosomes occurs with maternal aging and 4) the role of mitochondria in loss of oocyte competence. Information gained from studying the effects of follicular and maternal aging has broad clinical implications and is germane to the development of efficient assisted reproductive techniques for animals and humans. We anticipate that findings from the proposed work will allow direct improvements of existing reproductive management techniques in cattle such as, fixed-time artificial insemination, superovulation and embryo transfer.