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. Sub-optimal fetal organ growth and development are major problems associated with increased neonatal death and long-term morbidity. Underlying mechanisms are poorly understood. Whilst primary causes are diverse, poor fetal development is generally secondary to fetal nutrient restriction. Rodent and sheep studies provide insight but parallel nonhuman primate data are minimal. The overall P01 goal is to study effects of global maternal nutrient restriction: restricted mothers eat 70% feed eaten by ad lib controls (CTR). We hypothesize that exposure of fetal baboons to nutrient restriction adversely impacts growth and key cellular processes in placenta, fetal brain and kidney. We hypothesize: 30% global maternal nutrient restriction 1: impairs growth;2: impairs angiogenesis;3: impacts the IGF system;4: alters cellular nutrient sensing;5. influences programmed cell death, in a fetal sex and developmental stage specific manner. The three projects are: Project 1 ?Nutrient Restriction: Baboon Placental Growth and Function;Project 2 ?Nutrient Restriction: Fetal Baboon Brain Development;Project 3 ?Nutrient Restriction: Fetal Baboon Renal Development. We use a unique combination of approaches to evaluate maternal nutrient effects on development of placenta and fetal brain and kidney, key organs for adult health. This P01 addresses National Children's Study goals. The mammalian organism passes more milestones during in utero development than any other time of life. Sub-optimal conditions in utero alter placental function and brain and kidney development. Our studies will help determine mechanisms by which conditions experienced in the womb predispose to high blood pressure, obesity and diabetes in later life. Clinicians will use the information to understand optimal life style and diet in pregnancy.
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