Fundamental questions regarding the long-term health of children conceived in vivo during poor maternal health or adverse lifestyle choices, or conceived ex vivo in the course of infertility treatment, remain unanswered and are logistically difficult to resolve. The relationship between human fetal development and the risk of adult onset diseases, including Type II diabetes and cardiovascular disease, has been well described. Our laboratory and others have shown, in animal models, that the external microenvironment surrounding the early embryo significantly influences subsequent fetal development (""""""""embryonic programming""""""""). What remains unclear is the association between embryonic programming and potential risks of adult onset disease. In addition, the influence of the microenvironment during oocyte maturation, on embryonic programming and fetal development, is very poorly understood. Recent evidence implicates that some of the effects of adverse oocyte and embryo microenvironments are mediated by disturbed methylation of imprinted genes. Our previous work suggests that altered methylation alone cannot account for the range of fetal phenotypes observed. Our hypothesis is that adverse micro environments cause cellular stress within oocytes and embryos, which significantly induces a range of molecular and biochemical responses that impinge on embryo growth and implantation events, leading to an altered fetal phenotype. Several different approaches, all utilizing established animal models, will be used to test this hypothesis. These are: (1) determining the effect of cellular and molecular consequences of hypoxic stress on follicular enclosed oocytes, (2) describing the effect of hypoxia-induced gene expression in embryos on fetal development, (3) determining the role of nitrogenous nutrition during embryo development in eliciting ammonia-mediated stress, and (4) elucidating the cellular and molecular mechanisms within early embryos through which the growth factor milieu influences fetal development and neo-natal outcomes. By understanding the effect of the microenvironment on cellular and molecular behavior of oocytes and embryos, stress-induced responses can be minimized, improving the developmental outcomes for both mothers and babies. This knowledge will also assist health professionals develop strategies to reduce the risk of adult onset diseases caused by perturbed early development.
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