# Dysregulation of maternal immunity during pregnancy by pregravid obesity

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2024 · $445,947

## Abstract

Successful pregnancy requires carefully coordinated changes in the immune system that facilitate placentation,
promote fetal tolerance and growth, and induce labor. Deviations from this tightly regulated “pregnancy
immunological clock” can lead to as pre-eclampsia and complications during labor. The rates of obesity amongst
women of childbearing age have increased at an alarming rate, making it one of the most common comorbidities
during pregnancy. Previously published studies and our preliminary data indicate an enhancement of monocyte
response to LPS between 12 and 37 weeks of gestation Importantly, our preliminary analyses indicate that
maternal pregravid body mass index (BMI) >30 abrogates this pregnancy-associated monocyte activation. This
observation provides a potential explanation for the increased susceptibility to infections and poor wound healing
outcomes observed in obese pregnant women. We hypothesize that chronic low grade inflammation
induced by pregravid obesity disrupts the gestational age dependent monocyte activation, skewing them
to an immunotolerant phenotype. Additionally, given that macrophages in the decidua are recruited from
circulating monocytes, we will investigate the burden of obesity on phenotype and function of decidual
macrophages. We further hypothesize that pregravid obesity results in a hyper-inflammatory phenotype
within decidual macrophages. We will employ a multi-dimensional approach to test these hypotheses. The
novelty of this application lies in the systems biology approach that integrates phenotypic, functional, and
genomic readouts longitudinally in peripheral blood and at term in the placenta. Completion of the proposed
experiments will reveal the molecular mechanisms that explain progressive changes in monocyte activation over
the course of healthy pregnancy, and how that is disrupted with obesity.

## Key facts

- **NIH application ID:** 10907402
- **Project number:** 5R01AI145910-06
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Ilhem Messaoudi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $445,947
- **Award type:** 5
- **Project period:** 2019-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10907402

## Citation

> US National Institutes of Health, RePORTER application 10907402, Dysregulation of maternal immunity during pregnancy by pregravid obesity (5R01AI145910-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10907402. Licensed CC0.

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