Dr. Perrie O’Tierney-Ginn, MIRI PI, has received a Tufts Institute for Global Obesity Research (TIGOR) Pilot award for her study entitled “Placental mediation of maternal obesity impact on neonatal metabolism: a multi-omics approach.”
Over one in five women in the US begin pregnancy with obesity (body mass index > 30 kg/m2). Obesity during pregnancy increases the risk of developing serious complications such as gestational diabetes, preeclampsia and preterm birth, in addition to elevating the risk of future disease for the offspring, such as cardiometabolic disease, autism, attention deficit hyperactivity disorder, and obesity. The seed of these conditions that manifest later in life may be sown in utero as tissues are forming and metabolic pathways are developing. Indeed, at birth neonates born to women with obesity are insulin resistant, have greater levels of inflammatory cytokines, and on average higher fat mass than infants born to women without obesity. Thus offspring of obese women may have altered metabolic profiles at birth, which enhance their susceptibility to environmental and nutritional challenges later in life that manifest in disease and greater death rates. The placenta is the interface between the mother and fetus throughout pregnancy and, though long thought a passive channel for maternal nutrients, it plays an important role as nutritional gatekeeper – sending poorly understood signals to the mother to manipulate her metabolism (e.g. decrease insulin sensitivity) in order to free up more nutrients for uptake and transport, and modifying fetal nutrient delivery via metabolism and storage. Thus, the crosstalk between the placenta and mother is critical for fetal nutrient delivery, growth and future disease risk.
Importantly, not all women with obesity give birth to babies with high fat mass, indeed there exists a wide range in adiposity levels among women with and without obesity. Interestingly, babies born with lower adiposity may also have a lower risk of future cardiometabolic disease, though the factors underlying these variations in fetal fat accrual and their association with long-term health remain unclear.
The placenta produces miRNA which can be selectively released into the maternal circulation, impacting gene expression in peripheral tissues, and are potentially a critical feature of maternal – placental – fetal communication. Our preliminary data show that several placental miRNA are impacted by maternal BMI and associated with neonatal adiposity. One miRNA may bind dozens of mRNA transcripts, while one transcript may be targeted by multiple miRNA – thus we need complementary mRNA data to perform a more comprehensive analysis and interpretation of the networks involved in fetal fat accrual. The goal of this project is to create placenta-specific networks to identify miRNA-mRNA interactions associated with neonatal metabolic profiles and fat accrual.
To read more about Dr. O’Tierney-Ginn’s research, click here >