Mother Infant Research Institute (MIRI)

Perrie O’Tierney-Ginn, PhD is a Principal Investigator in the MIRI. Dr. O’Tierney-Ginn’s overall interest is to understand the effect of the maternal nutritional environment (metabolism, diet, body composition) on placental function, and fetal nutrient delivery and growth. Dr. O’Tierney-Ginn’s work is funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Please visit her external lab website at www.placentascience.com for more information.

The overall goal of our research is to understand how placental function is altered by the maternal environment, and how these changes affect fetal growth and fat deposition. This important area of investigation elucidates mechanisms by which babies’ growth in the womb (organ development, fat accrual, lean tissue growth) can modify their metabolism, cardiovascular function, neurological development, and their risk of future disease. This concept is referred to as the Developmental Origins of Health and Disease hypothesis and is the major focus of our research.

Lipids are critical for proper fetal development (think cell membranes!), but the fetus is unable to synthesize lipids at the rate required to fulfill its developmental requirements. The placenta is not capable of making these essential fatty acids either, and so the fetus relies on maternal supply and placental transfer of these critical nutrients for development. Thus, changes to placental fatty acid transport have serious implications for fetal growth and long-term health.

We have found that placentas from 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 lead to impairments in 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.

Publications:

Brass et al. Placental oleic acid uptake is lower in male offspring of obese women. Placenta, 2013
O’Tierney-Ginn et al. Sex-specific effects of maternal anthropometrics on body composition at birth. Am J Obstet Gynecol, 2015.
Calabuig-Navarro et al. Effect of maternal obesity on placental lipid metabolism. Endocrinology 158 (8), 2017.
Calabuig-Navarro et al. Effect of omega-3 supplementation on placental lipid metabolism in overweight and obese women. Am J Clin Nutr, 2016.

The overall 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 potierneyginn@tuftsmedicalcenter.org. 

High adiposity at birth is associated with poor metabolic outcomes and 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 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 study is to identify placental miRNA expression profiles associated with alterations in maternal insulin resistance (IR) throughout pregnancy resulting in high neonatal adiposity. We hypothesize that placentas of high adiposity infants express distinctive miRNAs that affect maternal post-receptor insulin signaling, resulting in high maternal insulin resistance.