# Admin Supplement - Immune Tolerance Dysfunction in Pregnancy due to Ambient Air Pollution Exposure

> **NIH NIH R01** · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · 2024 · $103,232

## Abstract

Parent R01 Research Summary: Pregnancy is a state of constant growth, proliferation, and modification in the
immune system between mother and fetus. For this reason, the maternal immune system is at higher risk for
exposures of toxicants during pregnancy. More specifically, toxicants from ambient air pollution are numerous
and many are absorbed directly from the lungs into the blood stream, resulting in concentrations of toxicants
increasing in pregnancy vs. no pregnancy. We hypothesize that exposure to ambient air pollution, specifically
particulate matter less than 2.5 M (PM2.5), could increase the likelihood of immune dysregulation in pregnant
women during, and in the short- and long-term periods after pregnancy. We will test this by the use of an extant
set of samples already collected and stored from a prior NIEHS funded study (PO1). These stored samples are
from cohorts (pregnant vs. non-pregnant) living in Fresno, CA continuously for more than 10 years in which
individual estimate exposures of PM2.5 (and other pollutants) have been quantitated using validated and
published methods. We have stored 200 blood samples during the 2nd trimester of pregnancy, and longitudinal
samples from the mothers (at birth, at 1 yr post birth, and at 3 yrs post birth). We also have stored samples from
an age matched set non-pregnant, non-parous females from the same area (n=200). Of the n=400 individuals,
approximately 50% live in high vs. 50% live in low PM2.5 exposure areas. Leveraging this unique dataset, we
hypothesize that the immune system (after a single pregnancy) —with a specific focus on regulatory T cells or
Treg--- will be significantly dysregulated in cell subsets, gene expression, T cell receptor, and cytokine responses
in pregnancy vs. no pregnancy and that the extent of this dysregulation will be worsened by exposure to PM2.5.
In addition, we will test if these mechanistic differences are driven by underlying epigenetic changes. Moreover,
the experimental design, which is longitudinal and covers year-to-year time points will be used to test exploratory
hypotheses surrounding sustainability of these changes since we have collected short term vs. long term time
points after pregnancy. Supplement Research Summary: The extent of PM2.5-induced gene expression changes
in B-cells and Monocytes during pregnancy vs. no pregnancy is unknown. Therefore, we will conduct global gene
expression profiling of monocytes and B-cell subsets and perform the comparative transcriptome analysis on
sorted monocytes and B-cells from maternal blood vs. cord blood exposed to high vs. low PM2.5 levels (Subaim
1b). Our primary hypothesis is that during pregnancy high exposure to fine particulate matter PM2.5 modulates
the epigenetic mark on maternal immune system, by inducing cell type specific epigenetic modifications. To
determine the mechanism of PM2.5 mediated changes in pregnancy, we will perform integrative multi-omics
analysis and reconstruct the regulatory map of...

## Key facts

- **NIH application ID:** 10939490
- **Project number:** 3R01ES032253-04S1
- **Recipient organization:** HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH
- **Principal Investigator:** Kari C. Nadeau
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $103,232
- **Award type:** 3
- **Project period:** 2020-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10939490

## Citation

> US National Institutes of Health, RePORTER application 10939490, Admin Supplement - Immune Tolerance Dysfunction in Pregnancy due to Ambient Air Pollution Exposure (3R01ES032253-04S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10939490. Licensed CC0.

---

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