# Gestational diabetes pathophysiology uncovered by placental transcriptomics

> **NIH NIH R01** · HARVARD PILGRIM HEALTH CARE, INC. · 2022 · $649,474

## Abstract

Summary abstract
During pregnancy, women experience major physiologic changes in glucose regulation that are regulated by
the placenta. In some pregnant women, regulation between insulin sensitivity and secretion is imbalanced,
leading to gestational diabetes mellitus (GDM). GDM is the most common metabolic disorder in pregnancy and
leads to complications in both mothers and offspring during pregnancy and long afterwards. Better
understanding of the placental role in gestational glucose regulation is necessary to identify early biomarkers
that predict GDM, and for the development of novel therapeutic agents to influence insulin secretion and insulin
sensitivity, the two major pathophysiologic determinants of diabetes inside and outside of pregnancy..
We propose to conduct placental genome-wide transcriptomic studies using the most recent methods for RNA-
sequencing and cutting-edge technology for miRNA sequencing. Placenta samples (n=662) were carefully
collected in a population-based prospective cohort of pregnant women called Gen3G. We have collected
refined phenotypes and plasma samples in 809 Gen3G women across gestation, including oral glucose
tolerance tests allowing us to characterize their insulin secretion, insulin sensitivity, and objectively diagnosed
GDM. For identified miRNA associated with insulin secretion in vivo, we will test whether they can stimulate
insulin secretion in in vitro validated β-cell models. For identified miRNA associated with insulin sensitivity, we
will test whether they can influence glucose-uptake in in vitro adipocytes models. After meticulous selection of
the most promising transcripts from our GDM vs normoglycemic women, we will develop assays to detect
secreted proteins in maternal plasma collected at 1st trimester. We will test associations between newly
identified placenta-specific secreted proteins (ELISA or Mass Spectrometry) and miRNA (RT-qPCR) detectable
in plasma at 1st trimester with GDM incidence. We will replicate our findings in two prospective multi-ethnic
cohorts of pregnant women.
This proposal leverages the richness of the unique Gen3G cohort, including placenta samples carefully
collected and preserved for transcriptomic studies, refined phenotypes of glucose regulation and plasma
samples across gestation. The team of investigators assembled for this application has substantial expertise
and previous experience to conduct each step of the proposed study. Finally, our transcriptomic results will be
rapidly available to the wider scientific community on the highly accessed GTEx portal, as we will follow all their
standard procedures for our sequencing.

## Key facts

- **NIH application ID:** 10428612
- **Project number:** 5R01HD094150-05
- **Recipient organization:** HARVARD PILGRIM HEALTH CARE, INC.
- **Principal Investigator:** Marie-France Hivert
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $649,474
- **Award type:** 5
- **Project period:** 2018-09-17 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10428612

## Citation

> US National Institutes of Health, RePORTER application 10428612, Gestational diabetes pathophysiology uncovered by placental transcriptomics (5R01HD094150-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10428612. Licensed CC0.

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