It is now clearly recognized from egg donation studies that it is the egg and not the reproductive tract that is the cause of reduced fertility or infertility. Remarkably, the molecular underpinnings of what constitutes an egg of """"""""high"""""""" quality are essentially unknown.
Specific Aim 1 will test the hypothesis that a specific pattern of gene expression characterizes eggs of high quality by using suppression subtractive hybridization to identify genes that are differentially expressed in meiotically and developmentally competent high quality mouse eggs. These genes will be used to construct an """"""""oocyte chip"""""""" that will be used to ascertain if a specific set of these genes is mis-expressed, or inappropriately expressed, in oocytes whose developmental competence is compromised, e.g., oocytes that develop during in vitro culture; oocytes derived from small antral follicles, oocytes obtained from hyperstimulated mice, and oocytes obtained from aged mice. The Fetal Origins of Adult Disease hypothesis posits that specific diseases in the adult are the result of the fetus's adaptations in utero to maternal under nutrition or malnutrition. This hypothesis may extend to the preimplantation stage, since reducing protein intake during this time in the rat results in such long-term changes, and the culturing of preimplantation embryos leads to offspring that exhibit altered behavior.
Specific Aim 2 will test the hypothesis that low quality eggs give rise to offspring that exhibit perturbations in behavior by analyzing these offspring with a battery of behavioral assays. Treatment of human infertility with Assisted Reproductive Technology (ART) entails embryo culture that can result in changes in gene expression. Even eggs of high quality (and the resulting preimplantation embryos) that are used in ART may be at risk simply due to embryo culture conditions.
Specific Aim 3 will test the hypothesis that modifications of culture conditions can alleviate the effect of embryo culture on the culture-associated perturbations observed in gene expression and behavior in the offspring. Results of these experiments will establish the molecular basis of egg quality and will provide critical information regarding the effect on behavior in offspring derived from low quality eggs, as well as the effect of ART procedures on gene expression and behavior.
