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 of embryo development. More than 95% of oocytes (eggs) become fertilized after insemination (conception) but >50% 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 (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 reproductive aging and documented that mother's age (maternal aging) is associated with a decrease in oocyte competence. We have also discovered that oocyte competence is compromised when the life-span of a growing follicle is prolonged by as little as 3-4 days (follicular aging). We propose to address the fundamental biological question: How does oocyte dysfunction occur and which molecular pathways are responsible for the effects of follicular and maternal aging? Our working hypothesis is that the loss of oocyte competence is caused by similar cellular changes during maternal and follicular aging. The specific objectives of this research are to determine 1) the precise molecular pathways in the granulosa cells of the ovulatory follicle that are either up- or down-regulated during maternal and follicular aging, 2) the role of theca cells in loss of oocyte competence, and 3) which specific genes and molecular pathways in the aged oocyte are responsible for the developmental failure. 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 and humans. We anticipate that our results will allow direct improvements of artificial insemination, superovulation and in vitro embryo production techniques in cattle.