Grants and Contributions:

Grant or Award spanning more than one fiscal year. (2017-2018 to 2022-2023)

The most critical period influencing the success or failure of pregnancy is the first 7 days of embryo development. More than 95% of oocytes (eggs) become fertilized after insemination (conception) but >50% of the embryos fail to develop. The reason for this high rate of failure is unclear, but is associated with quality of the oocyte and the ovarian follicle in which it grows (a follicle is a fluid-filled structure composed of granulosa and theca cells). The long-term objective of my research program is to elucidate the endocrine, cellular and molecular mechanisms that affect an oocyte's ability to develop into a healthy embryo (i.e., oocyte competence). Studies proposed herein are based on a fruitful line of research established in 2002 and made possible with previous NSERC funding. My research team at the University of Saskatchewan has developed the bovine model for the study of follicular and reproductive aging. By extending the duration of treatment with follicle stimulating hormone (FSH), we are able to enhance the oocytes' ability to produce embryos. But, oocyte competence is compromised when the life-span of a growing follicle is prolonged by as little as 3-4 days (follicular aging) without proper FSH support. We have also documented that cows aged ≥13 years (maternal aging) have a marked decrease in oocyte competence compared to their young daughters. Interestingly, oocytes obtained from calves ≤4 months of age (early pre-pubertal age) also have lower developmental competence. It appears that oocytes attain full competence when the calf is about 10 months of age (peri-pubertal age). The focus of my research program for the next 5 years is to understand the cellular and endocrine pathways that influence the oocyte competence during the pre-pubertal period. Our working hypothesis is that the endocrine milieu and local ovarian factors responsible for poor developmental competence of oocytes during the pre-pubertal period are unique and distinct from those that cause the loss of competence during old age. Our objectives are to 1) determine the effects of a longer period of gonadotropin support on follicular dynamics and oocyte competence during the pre-pubertal aging, and to examine the 2) molecular pathways involved in follicular function and 3) responsiveness of hypothalamic-pituitary-ovarian axis during the pre-pubertal development. Information gained from these studies has broad implications regarding the biology of aging and is germane to the development of efficient assisted reproductive techniques for animals. We anticipate that our results will allow direct improvements of superovulation, in vitro embryo production and progeny testing in cattle. On a longer time–scale, my NSERC Discovery program on follicular and maternal aging will continue to expand our basic understanding of mechanisms that imbue competence of the oocyte to develop into an embryo in mammalian species.