Grant: Discovery Grants Program - Individual

The most critical period influencing the success or failure of pregnancy is the first 7 days of embryonic life. More than 95% of the eggs (oocytes) become fertilized but only 30-50% of bovine oocytes produce embryos in vitro. The reason for this high rate of attrition is unclear but is associated with the intrinsic status of the oocyte and the follicle in which it matures. The long-term objective of my research program is to elucidate the hormonal, cellular and molecular mechanisms that facilitate or hamper an oocyte's ability to develop into a viable embryo. This grant application is a logical continuation of my four successive NSERC Discovery grants. Our work has shown that an oocyte's ability to develop into a blastocyst (oocyte competence) is affected by age of the female; it waxes and wanes during the prepubertal period and late senescence. Our overarching hypothesis is that the suboptimal endocrine milieu and local ovarian factors responsible for poor developmental competence of oocytes during the prepubertal period are unique and distinct from those during follicular aging in adult cows and after maternal aging. By integrating our current understanding of endocrine interactions and follicle function, we are now poised to address the fundamental biological question: How does an incompetent oocyte acquire functional competency during prepubertal development and which cellular pathways are involved in the process? The focus of my program for next 5 years is to understand the cellular and endocrine pathways associated with attainment of oocyte competence in calves during the prepubertal period and immediately thereafter. During the ongoing NSERC grant, we have discovered that the competence of prepubertal oocytes can be enhanced by optimizing the growth of follicles with follicle stimulating hormone (FSH) for 4 to 7 days. However, we do not yet fully understand the effects of gonadotropin modulations as the sensitivity of hypothalamus-pituitary-ovarian axis changes from early prepubertal period to onset of puberty. For the next 5 year, our three short-term objectives are to 1) elucidate the effect of hormonal modulations on follicular dynamics and oocyte competence during the prepubertal period, 2) characterize the molecular pathways and follicular markers of oocyte incompetence during the prepubertal period and 3) assess if factors affecting oocyte competence differ between the prepubertal period and old age. Calves are available at the University farm, oocyte recovery and embryo culture techniques are routine procedure in my laboratory and bioinformatics platform is available through the newly-funded CFI infrastructure grant. We anticipate that findings from the proposed work on oocyte competence, follicular function and endocrine feedback mechanisms will provide a fundamental understanding of underlying mechanisms of ovarian function in cattle that will have broad implications on fertility management in food animals and other mammals.