DESCRIPTION (provided by applicant): Maternal obesity during pregnancy is common and is associated with increased obstetric, neonatal, and childhood risks. Of growing concern is maternal nutrition during pregnancy due to the global obesity epidemic and the availability and consumption of a high calorie/high fat Western style diet (HFD). The nonhuman primate (NHP) shares developmental ontogeny similar to human fetuses including placental function, and the full spectrum of metabolic disease when placed on a HFD diet making it an invaluable model for translatable studies. In this animal model we are able to distinguish the relative contribution of maternal diet and metabolic health, something that is difficult in human cohorts. Our recent studies directly link HFD consumption in this well characterized NHP model with a reduction in uteroplacental perfusion and increased placental injury suggesting that a Western style diet may have a significant independent impact on the adverse obstetric and neonatal consequences reported in the obese human population. Since the placenta regulates nutrient exchange from mother to fetus, it occupies a central role in mediating the adverse obstetric risks associated with the obese gravidae. Current assessments of placental function, both clinical and research are limited by an inability to link placental perfusion with placental pathology and nutrient transport. Our objectives are to understand the consequences of altered placental blood flow on placental development and lipid transport in our NHP model. We have developed a novel Dynamic Contrast Enhanced-MRI (DCE-MRI) technique that quantifies placental blood flow directly to the transfer unit of the placenta, the cotyledon. We propose to use DCE-MRI, complemented by in vitro assays of lipid transport in individually identified cotyledons, to correlate blood flow with lipid uptake. Secondarily, we will simultaneously utilize Contrast Enhanced-Ultrasound (CE-US) as a complementary imaging technique to DCE-MRI that can be more readily implemented in the clinical setting as a diagnostic tool for placental dysfunction. Fresh placental villous explants will be used for radiolabeled fatty acid uptake studies. Fatty aci uptake in each cotyledon will be correlated with placental perfusion as quantified by DCE-MRI and CE-US. Placental tissue will be assessed for pathological evidence of ischemia and insufficiency. In addition, we will characterize components of the fatty acid transport pathway in placental homogenate isolated from individually sampled cotyledons, and measure maternal and fetal levels of triglycerides and nonesterified fatty acids. In summary, our novel approach uses advanced imaging in a physiologically relevant animal model to link placental perfusion with a vital functional endpoint, and demonstrate the feasibility of using advanced imaging techniques to identify placental insufficiency for both basic science and clinical implementation.
|Effective start/end date||4/5/13 → 3/31/16|
- National Institutes of Health: $255,150.00
- National Institutes of Health: $218,750.00