PLACENTOMAL VASCULAR ADAPTATIONS TO EARLY MATERNAL NUTRIENT RESTRICTION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We have extended our investigations during the course of the grant to study the impacts of maternal overnutrition as well as undernutrition on the placenta and fetus. The United States is experiencing an obesity epidemic which increasingly involves women of child bearing years. Increased pre-pregnancy maternal weight correlates with increased offspring weight and the potential for persistent and damaging consequences resulting from changes in body composition and developing tissue and organ function. The sheep is a powerful, unique model to study intrauterine environmental effects on placental and fetal development. There is an unparalleled fetal data base on physiological systems in this model from highly regarded laboratories worldwide. Clinical studies show developmental problems in the fetal pancreas in children born to obese pregnant women that lead to abnormalities of fetal growth and body composition. Offspring of obese mothers are more prone to chronic conditions such as obesity and diabetes that greatly impairs their life-time health. There is currently a lack of knowledge regarding the mechanisms whereby maternal obesity modifies placental and/or fetal development and function, or how this leads to health problems after birth. We have developed a model of maternal obesity in the sheep and are investigating diet induced changes in placental structure (i.e. composition, vascularity and placentomal type) and function (vascular sensitivity to vasoactive agents, placental nutrient transportors, and nutrient delivery to the fetus). Impact of maternal obesity on fetal pancreatic structure and function and fetal tissue (i.e. skeletal muscle, adipose, etc.) insulin sensitivity are also under investigation.