High adiposity at birth is associated with poor metabolic outcomes and increased risk of obesity in childhood and adult life. Maternal obesity (body mass index >30 kg/m2) is associated with increased fetal adiposity, but not all obese women have obese babies. Non-Hispanic Black or African American women experience a disproportionate amount of pre-pregnancy obesity and fetal growth restriction, in addition to other poor pregnancy outcomes ? yet are underrepresented in perinatal research studies investigating the effects of maternal metabolism on fetal growth. Maternal insulin sensitivity is a key predictor of fetal fat accrual, but the mechanisms regulating insulin signaling during pregnancy are unknown. We have found that maternal insulin sensitivity improves 120% following delivery of the placenta, suggesting a placental factor may regulate insulin signaling during pregnancy. As placental growth and gene expression is sensitive to maternal insulin levels in early pregnancy, and correlated to adiposity at birth, we propose that maternal-placental crosstalk is key to fetal growth regulation. Placental-derived microRNAs (miRNA) regulate post-transcriptional gene expression in maternal tissues, and are detectable in maternal plasma throughout pregnancy. Thus, miRNAs may provide both a mechanism for maternal-placental crosstalk, and novel indicators of women at risk of high fetal fat accretion. The overall goal of this supplement is to utilize a well-phenotyped, racially-diverse birth cohort to identify placental miRNA expression profiles associated with alterations in maternal insulin resistance throughout pregnancy resulting in high neonatal adiposity. We hypothesize that placentas of high adiposity infants have a distinctive miRNA expression profile affecting maternal insulin signaling, resulting in high maternal insulin resistance. To test this hypothesis, we will utilize pre-collected samples from our birth cohort. The cohort consists of four groups: lean and obese women who delivered high or low adiposity offspring. These women all had healthy pregnancies, were not diabetic, and recruited at time of scheduled cesarean section where maternal blood, insulin sensitivity data and placental tissue were collected, and neonatal adiposity was measured. This supplemental study will determine whether placental miRNA expression within these four adiposity groups is affected by maternal race/ethnicity, as racial disparities in fetal growth and body composition have been reported. Upon completion of the proposed studies we will have determined: 1) the identity of miRNAs that are associated with high neonatal adiposity in placentas of lean and obese non-Hispanic Black and White women; 2) the relationship between circulating levels of these miRNA and maternal insulin sensitivity at term. Identification of markers of altered placental function affecting neonatal adiposity, detectable non-invasively in pregnancy, will improve our screening for pregnancies at risk of excessive fetal fat accretion and may lead to specific therapies based on the underlying physiology.
High adiposity at birth is associated with increased risk of obesity, diabetes and heart disease later in life. Maternal insulin sensitivity is one of the strongest predictors of her baby?s fat mass at birth, but few studies have assessed these relationships in diverse populations. The proposed supplement will help us understand how the placenta regulates maternal insulin sensitivity throughout pregnancy and how this impacts neonatal growth and fat deposition.
