I am committed to a career in academic medicine, and my five-year career goal is to become an independent investigator in the areas of maternal body composition, maternal metabolism, placental nutrient transport, and fetal growth. My long-term career objective is to build a strong translational research program to study the effect of maternal fat and muscle mass on placental function, neonatal development, and the offspring's risk of future cardiovascular disease. I have completed my clinical training in maternal-fetal medicine, a Master of Clinical Research degree, and have received valuable basic training in molecular techniques. Additional training is required however before I can achieve my career goal of becoming an independent investigator in maternal-fetal-placental health. The proposed training program has been designed to provide training in: 1) placental physiology and developmental health, 2) maternal metabolism and 3) project management and leadership skills. Oregon Health and Science University is an ideal environment for this training. It offers is strong reputation as a leading biomedical research and training institution;the Center for Developmental Health is internationally recognized for its work in fetal physiology and the developmental origins of health and disease;and the Oregon Clinical and Translational Research Institute (OCTRI) is dedicated to the development of successful young investigators. One in five women who deliver in the United States is obese. Babies born to obese women are at risk for being at the extremes of birth weight (>4500g or <2500g) and developing chronic diseases as adults. Our preliminary data show that increased maternal fat: fat free mass ratio is associated with increased placental inflammatory cytokines and abnormal placental nutrient transporter expression. Due to their rapid growth in utero, boys are at a greater risk of undernourishment. The overall goal of this proposal is to determine the degree to which maternal fat: fat free mass ratio impacts placental inflammatory cytokine levels and nutrient transporter expression and activity in order to better understand how maternal obesity and fetal sex impacts fetal growth. These studies will help determine the effect of maternal obesity, fetal sex, and inflammatory cytokines on placental nutrient transport and hopefully provide future interventional targets to improve the health status of women and their children. Upon completion of the proposed studies, we will have measured: 1) maternal fat: fat free mass ratio, maternal markers of glucose and amino acid metabolism, and maternal, fetal, and placental inflammatory cytokine levels in lean and obese mothers;2) transporter gene and protein expression levels in the placenta as well as glucose uptake in placental explants in vitro according to the sex of the fetus in lean and obese mothers;3) amino acid and glucose levels in umbilical cord plasma and offspring fat: fat free mass ratios at birth and in the first year of life.
The prevalence of obesity in women who give birth in the US is 1 in 5, which is associated with severe health consequences for both mother and child. Abnormal fetal growth due to maternal obesity is known to put the child at a higher risk of cardiovascular disease in later life. The proposed studies will help us understand how obesity during pregnancy alters the placental transfer of nutrients from mother to child and how this impacts neonatal growth.