# Epigenetics of decidual inflammation

> **NIH NIH P50** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $411,869

## Abstract

The decidua is thought to play a central role in pregnancy by providing trophic and structural support for the
placenta. In addition, recent work has indicated that it actively inhibits tissue reactions that, while normal for
other tissues, would be problematic for pregnancy. One particularly important example is the suppression of
acute inflammatory reactions, including ones that could recruit activated T cells from the blood. This proposal
investigates the extent to which such suppression is due to the epigenetic silencing of inflammatory target
genes in decidual stromal cells (DSCs). Specifically, we seek to gain insight into how repressive histone
modifications generated in DSCs upon their differentiation from endometrial stromal cells (ESCs) prevent gene
expression that would otherwise engender maladaptive inflammatory and immune reactions. Importantly,
inflammation itself is known to regulate the generation and erasure of histone marks in a variety of non-uterine
contexts, and once altered, the histone configuration of an affected gene locus can persist for extended
periods of time. Thus, we will also test the hypothesis that pre-implantation uterine inflammation can affect
post-implantation pregnancy outcomes in part by permanently altering the histone configurations of select gene
loci in endometrial stromal cells. These configurations might be detrimental to early pregnancy to the extent
they allow for maladaptive inflammatory reactions, but they also might be advantageous to the extent that they
limit such reactions. In Aim 1, we will determine, in genome-wide fashion and in both mice and humans, how
repressive histone mark (H2AK119Ub, H3K9me2 and H3K27me3) distributions change in ESCs upon
decidualization. This Aim will assess ESCs from endometrial biopsies of non-pregnant women and DSCs from
first trimester decidual specimens. The specimens will moreover come from normal women and women with
endometriosis, thus providing insight into how endometrial inflammation influences mark generation in vivo. We
will perform parallel studies in mice, inducing uterine inflammation in the pre-implantation period to determine
its effects on histone mark generation in post-implantation DSCs. Aim 2 then utilizes genetic mouse models in
order to functionally dissect the consequences of disrupted mark generation on the early decidua, including
whether it now mounts overly robust immunological responses that might impair fetoplacental development.
Lastly, Aim 3 will identify the mechanisms regulating the genome-wide distributions of repressive histone
marks in primary human endometrial stromal fibroblasts induced to decidualize in vitro. This Aim will directly
test the effects of pre-decidual inflammation, thus creating models to dissect the effects of endometrial
inflammation uncovered in Aim 1. Together we expect our studies to provide insight into key regulatory circuitry
that underpins the immunological quiescence of the first trimester decidua, and ...

## Key facts

- **NIH application ID:** 10673396
- **Project number:** 1P50HD112034-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Adrian Erlebacher
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $411,869
- **Award type:** 1
- **Project period:** 2023-08-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10673396

## Citation

> US National Institutes of Health, RePORTER application 10673396, Epigenetics of decidual inflammation (1P50HD112034-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10673396. Licensed CC0.

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