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. The present proposal uses adult male and female baboons to produce 10 pregnancies to study the unwanted and harmful effects of obesity on the fetus and mother, by looking at effects of obesity on the placenta. Specifically the purpose of this study is to compare the physiology of lean vs obese baboons for specific differences in placental micro/macro structure and to correlate these with changes in insulin-like growth factor (IGF) system peptides (IGFI &II, their receptors and binding proteins) and differences in placental amino acid transport. Animals selected for lean body weight/BMI or high body weight/BMI will be fed ad libitum prior to and during pregnancy. At 165 ? 5 days of gestation, a terminal c-section will be performed and the fetus and dam will be euthanized with the placenta and selected maternal and fetal tissues obtained for study. It is expected that there will be significant differences: 1) in placental structure as revealed by stereology, 2) in amino acid transport measured by placental villous microvessicle transport using carbon 14-labeled methylaminoisobutyric acid uptake) and 3) IGF system peptides messenger RNA and protein measured by QRT-PCR, Western blot and immunocytochemistry. The expected outcomes are: increases in placental vascularization (length of the capillaries), number of immature villi and placental macrophages. We also expect to find increased placental amino acid uptake. Published data show that IGF-I is a nutrient sensitive peptide, thus we are expecting the over-expression of this molecule in the placenta. The expression of other IGF system peptides remains to be elucidated.
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