Influence of maternal diet on the developmental potential of the preimplantation embryo.
Journal of Nutrition, 137, .
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The cleavage-stage embryo is sensitive to environmental conditions that can change developmental potential, leading to altered fetal and postnatal phenotype. We have developed mouse and rat models in vivo to investigate the effect of a mild form of maternal protein undernutrition exclusively during egg cleavage on long-term developmental potential. Maternal low-protein diet (LPD) during embryonic development leads to significant alteration in fetal and postnatal growth, a sustained increase in systolic blood pressure during adult life, and a changed pattern of anxiety-related behavior compared with controls fed a normal-protein diet during the embryonic period. This long-term patterning of phenotype includes gender-specific components. The sensitivity of embryos in vivo is paralleled by a similar adverse programming of phenotype in response to in vitro culture conditions, demonstrated in several species. Given the health care implications of the data arising from these models, elucidation of underlying mechanisms contributing to environment-induced changes in embryo potential is essential. Studies to date indicate that complex interactions are mediated through altered cell signaling, homeostatic regulation, proliferation, and epigenetics. In vivo programming via maternal LPD may initiate through abnormal cross-talk between maternal and embryonic cells involving amino acid and growth factor signaling, which may lead to altered setting of metabolism and biosynthesis within the embryo. Our data further indicate that in response to poor maternal periconceptional nutrition, the embryo can induce adaptations in nutrient supply during later development via the visceral yolk sac to protect fetal growth. However, such adaptations can be inappropriate and contribute to adverse fetal and postnatal programming when maternal nutrient levels exceed those predicted. Epigenetic changes involving DNA methylation in control regions of growth- and metabolism-regulating genes, including imprinted genes, have been identified in response to embryo in vitro culture conditions and sustained maternal LPD during gestation, representing additional mechanisms contributing to changes in developmental potential
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