O'Tierney-Ginn Laboratory

Lipids are critical for proper fetal development, but the fetus is unable to synthesize lipids at the rate required to fulfill its developmental requirements. The placenta is incapable of making these essential fatty acids either, so the fetus relies on maternal supply and placental transfer of these critical nutrients for development. Thus, changes to placental fatty acid transport changes have serious implications for fetal growth and long-term health.

We have found that the placentas of obese mothers take up and metabolize lipids differently from those of lean mothers, and that this may depend on whether the fetus is male or female. Placentas of obese women store more fat, and their mitochondria do not metabolize fatty acids efficiently, which may impair energy production for other placental functions. Excitingly, we may be able to intervene and improve placental lipid metabolism with changes to maternal diet during pregnancy. We found that obese women who supplemented with fish oil during their pregnancy had lower placental lipid accumulation.

The goal of this study is to determine how maternal fat metabolism in early pregnancy programs placental lipid metabolism and a baby’s fat deposition. We hypothesize that obese women who have a high-fat metabolism in early pregnancy will have a unique lipid profile, and these lipids will act as “signals” to the developing placenta, programming placental lipid metabolism in early pregnancy and increasing lipid delivery to the baby and fat accrual. To test this hypothesis, we will recruit healthy women that we follow throughout pregnancy, measuring their fat metabolism, diet and body composition in early and again in late pregnancy. We will then measure placental lipid metabolism and their babies’ fat mass at birth.

This is an ongoing longitudinal cohort study in collaboration with the Human Nutrition Research Center at Tufts. For more information about the study, please contact Dr. O’Tierney-Ginn at perrie.f.otierney-ginn@tuftsmedicine.org.

High adiposity at birth is associated with poor metabolic outcomes and an increased risk of obesity in childhood and adult life. Maternal obesity is associated with increased fetal adiposity, but not all obese women have obese babies. 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 placenta delivery, suggesting a placental factor may regulate insulin signaling during pregnancy. As placental growth and gene expression are 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. Indeed, we have identified placental miRNA associated with alterations in maternal insulin resistance (IR) throughout pregnancy, and high neonatal adiposity, and are currently investigating their mechanism of action and target tissues.