Maternal Stress-Mediated Gene Expression Changes in the Mouse Placenta: A Mosaic Hypothesis of Epigenesi

For optimal growth, development, maturation, and survival of the embryo/fetus, successful development and function of the placenta is crucial. Evidence from both epidemiologic studies in humans and experimental investigation in laboratory animals has demonstrated that antenatal maternal stress (protein/caloric deficiency or excess, hypoxia, and other invidious influences) establishes the foundation in utero for disease in the adult offspring. Here we consider aspects of gene expression and the role of epigenetics in the murine placenta as a consequence of maternal stressors. The mouse, a species in which the genome has been sequenced, and in which studies can be performed in a controlled manner, is a valuable “model” for such studies. Although each individual maternal stress is characterized by up- or downregulation of specific placental genes, functional analysis reveals some patterns of expression common to the several forms of stress. Of critical importance, these stress-altered genes include those involved in DNA methylation, histone modification, microRNA alteration, cell cycle regulation, and related global pathways of relevance to epigenetics in the developmental origins of adult health and disease. We attempt to synthesize the data and information into a coherent whole, presenting a mosaic hypothesis of epigenetic mechanisms to account for the various responses and their manifestations.