# Placental miRNAs paracrine and endocrine roles in insulin sensitivity in pregnancy

> **NIH NIH R01** · TUFTS MEDICAL CENTER · 2024 · $577,364

## Abstract

Project Abstract
The physiological decrease in maternal insulin sensitivity during pregnancy is necessary to increase nutrient
availability for placental uptake and fetal delivery. When the decrease in insulin sensitivity is excessive, it results
in adverse pregnancy outcomes such as gestational diabetes leading to fetal macrosomia and hypoglycemia at
delivery, and long-term risk for development of diabetes in mother and offspring. The mechanisms regulating
insulin signaling during pregnancy are unknown. Maternal insulin sensitivity improves 120% within hours
following delivery of the placenta, suggesting a placental factor may regulate insulin signaling during pregnancy.
We have identified microRNAs (miRNAs) produced in the placenta that are associated with maternal insulin
sensitivity index in late pregnancy. We detected some of these placenta-expressed miRNAs in maternal
circulation as early as 8-12 weeks of gestation, suggesting they may be involved in the physiological adaptations
of maternal glucose metabolism beginning early in pregnancy. The overall goal of this study is to investigate
mechanisms by which selected candidate placental miRNA participate in the interplay between placenta and
glucose-insulin regulation during pregnancy. We hypothesize that miRNA produced in the placenta and regulated
by maternal glycemia, act locally and peripherally to manipulate maternal insulin sensitivity during pregnancy.
To test this hypothesis, we will leverage our existing perinatal cohorts which include longitudinal prospectively
collected plasma samples and insulin sensitivity index (ISI) data derived from oral glucose tolerance tests in the
first, second and third trimesters of pregnancy. We will also utilize in vitro human primary cellular models to
directly test the function of placenta-derived miRNA locally (paracrine actions in placenta) and in insulin-sensitive
peripheral tissues (endocrine actions). Upon completion of the proposed studies we will have determined: 1) the
local effect of placental miRNA related to maternal insulin sensitivity on placental gene expression and
function; 2) the peripheral effect of placental miRNA related to maternal insulin sensitivity on skeletal
myocytes, adipocytes and hepatocytes in vitro; 3) the regulatory role of hyperglycemia on placental
miRNA expression and release. A detailed understanding of the function and regulation of these placental
miRNA may provide us with novel targets for treatment of pathophysiological decreases in insulin sensitivity.

## Key facts

- **NIH application ID:** 10873280
- **Project number:** 5R01HD109206-03
- **Recipient organization:** TUFTS MEDICAL CENTER
- **Principal Investigator:** Marie-France Hivert
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $577,364
- **Award type:** 5
- **Project period:** 2022-08-16 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10873280

## Citation

> US National Institutes of Health, RePORTER application 10873280, Placental miRNAs paracrine and endocrine roles in insulin sensitivity in pregnancy (5R01HD109206-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10873280. Licensed CC0.

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