# Effects of Maternal Obesity on Offspring Immune System

> **NIH NIH R21** · STANFORD UNIVERSITY · 2020 · $199,003

## Abstract

Project Summary/Abstract
Obesity has reached epidemic proportions in the U.S, and recent studies have demonstrated that the children
of obese mothers are far more likely to become obese than the children of non-obese mothers. The
explanation for this association is unknown. Since obesity is associated with a widespread macrophage-
dependent inflammatory state, we hypothesize that obesity-associated factors in obese mothers cross the
placental barrier and adversely affect the fetal immune system. We further hypothesize that monocytes, which
constitute a substantial portion of immune cells in the developing fetus, are particularly sensitive to such
factors. Our preliminary data support this concept; we show that monocytes in the fetuses of diet-induced
obese mice are phenotypically altered relative to the same cells in the fetuses of non-obese mice fed a normal
diet. Therefore, in this proposal, in Aim 1 we will decipher the effects of maternal obesity on developing
monocytes in the liver and placenta at the phenotypic, functional, epigenetic and transcriptional levels.
Additionally, we will use mass cytometry in combination with our novel Scaffolds algorithm to analyze changes
of monocytes and other major immune cell populations in multiple tissues and at multiple time points in the
offspring of normal versus obese mice. In Aim 2, based on preliminary data showing that high-fat diet fed
female mice have increased levels of cholesterol and fatty acids, which can cross the placenta, we will directly
test the effects of these factors on fetal monocyte function. Upon completion of the proposed studies, we will
have identified maternal factors that affect fetal monocytes and potentially other immune cells, and we will
learn if their effects persist after birth.

## Key facts

- **NIH application ID:** 9913383
- **Project number:** 5R21HD098688-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** EDGAR G. ENGLEMAN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $199,003
- **Award type:** 5
- **Project period:** 2019-04-10 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9913383

## Citation

> US National Institutes of Health, RePORTER application 9913383, Effects of Maternal Obesity on Offspring Immune System (5R21HD098688-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9913383. Licensed CC0.

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