| Maternal malnutrition predisposes offspring to obesity, metabolic disorders and cardiovascular diseases in postnatal life. The placenta, as the only connection between the fetus and its mother, plays a critical role in mediating fetal intrauterine development. Both the placental vasculature and nutrient transport system are involved in delivering nutrients to support fetal growth. The placenta receives hormonal signals representing maternal nutrient and metabolic status, which may alter the development and functions of the placenta itself. We hypothesize that the placental vasculature, growth signaling pathways, nutrient transporters, and metabolic and immuno-homeostasis are altered in response to maternal malnutrition, and therefore affect fetal development. In the current thesis, two major animal models are presented to test the hypothesis, an obese (OB) overnourished pregnant ewe model and a nutrient restricted (NR) pregnant ewe model. The sheep placental exchange unit is called a placentome that is comprised of maternal caruncular and placental cotyledonary (COT) tissues. In both models, the COT placenta exhibits altered vascular development, nutrient transporters, and growth signaling at around mid-gestation to either limit (OB ewe model) or compensate (NR ewe model) fetal growth during the second half of gestation. COT inflammation is magnified in OB ewes, which results in chronic fetal inflammation that can potentially impair fetal organ development. Through investigations into postnatal offspring development, the altered placental functions demonstrated here have been confirmed to have impacts on adiposity, insulin resistance and glucose homeostasis and shall provide a significant amount of biomedical information to the mirrored human pregnancy complications. |
