# Placental mRNA profiles associated with maternal insulin resistance and fetal adiposity: maternal-placental crosstalk

> **NIH NIH R01** · TUFTS MEDICAL CENTER · 2020 · $436,296

## Abstract

Project Abstract
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. 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 utilize two well-phenotyped, racially-diverse birth cohorts
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 two birth cohorts.
The first cohort will consist 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. In a
second cohort, maternal blood and insulin sensitivity were measured in early and late pregnancy and placental
tissue was collected at term. In both cohorts, neonatal adiposity was measured. The term cohort will be used to
identify placental miRNAs associated with high neonatal adiposity, and the longitudinal cohort will be used to
validate these miRNA throughout pregnancy. 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 women; 2) the presence of these placenta-derived miRNAs in maternal plasma in early
and late pregnancy; 3) the effect of placenta-derived miRNAs on insulin signaling pathways in skeletal
muscle in vitro. Identification of markers of altered placental function affecting neonatal adiposity, detectable
non-invasively in early pregnancy, will improve our screening for pregnancies at risk of excessive fetal fat
accretion and may lead to specific therapies based on the underlyin...

## Key facts

- **NIH application ID:** 9873058
- **Project number:** 5R01HD091735-04
- **Recipient organization:** TUFTS MEDICAL CENTER
- **Principal Investigator:** Perrie F O'Tierney-Ginn
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $436,296
- **Award type:** 5
- **Project period:** 2017-03-10 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9873058

## Citation

> US National Institutes of Health, RePORTER application 9873058, Placental mRNA profiles associated with maternal insulin resistance and fetal adiposity: maternal-placental crosstalk (5R01HD091735-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9873058. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*