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.

Public Health Relevance

Maternal nutrition has a fundamental influence on pregnancy outcome and is of growing concern due to the worldwide obesity epidemic and the availability and consumption of a high fat/high calorie diet. In the obese mother the placenta develops under conditions of excess nutrients and inflammation leading to placental injury and altered fetal growth. Our new research initiative seeks to understand the consequences of consuming a high fat diet on placental development, focusing on the effect of alterations in placental blood supply on nutrient transfer to the baby using advanced imaging techniques.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Exploratory/Developmental Grants (R21)
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Pregnancy and Neonatology Study Section (PN)
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Ilekis, John V
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Oregon Health and Science University
Obstetrics & Gynecology
Other Domestic Higher Education
United States
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Roberts, Victoria H J; Lo, Jamie O; Lewandowski, Katherine S et al. (2018) Adverse Placental Perfusion and Pregnancy Outcomes in a New Nonhuman Primate Model of Gestational Protein Restriction. Reprod Sci 25:110-119
Salati, Jennifer A; Roberts, Victoria H J; Schabel, Matthias C et al. (2018) Maternal high-fat diet reversal improves placental hemodynamics in a nonhuman primate model of diet-induced obesity. Int J Obes (Lond) :
Roberts, Victoria H J; Lo, Jamie O; Salati, Jennifer A et al. (2016) Quantitative assessment of placental perfusion by contrast-enhanced ultrasound in macaques and human subjects. Am J Obstet Gynecol 214:369.e1-8
Schabel, M C; Roberts, V H J; Lo, J O et al. (2016) Functional imaging of the nonhuman primate Placenta with endogenous blood oxygen level-dependent contrast. Magn Reson Med 76:1551-1562
Frias, Antonio E; Schabel, Matthias C; Roberts, Victoria H J et al. (2015) Using dynamic contrast-enhanced MRI to quantitatively characterize maternal vascular organization in the primate placenta. Magn Reson Med 73:1570-8
Lo, Jamie O; Schabel, Matthias C; Roberts, Victoria H J et al. (2015) Vitamin C supplementation ameliorates the adverse effects of nicotine on placental hemodynamics and histology in nonhuman primates. Am J Obstet Gynecol 212:370.e1-8
Oh, Karen Y; Roberts, Victoria H J; Schabel, Matthias C et al. (2015) Gadolinium Chelate Contrast Material in Pregnancy: Fetal Biodistribution in the Nonhuman Primate. Radiology 276:110-8
O'Tierney-Ginn, P; Roberts, V; Gillingham, M et al. (2015) Influence of high fat diet and resveratrol supplementation on placental fatty acid uptake in the Japanese macaque. Placenta 36:903-10
Roberts, Victoria H J; Frias, Antonio E; Grove, Kevin L (2015) Impact of maternal obesity on fetal programming of cardiovascular disease. Physiology (Bethesda) 30:224-31