# The Role of SRF in Uterine Homeostasis

> **NIH NIH FI2** · U.S. NATIONAL INST OF ENVIRON HLTH SCIS · 2024 · —

## Abstract

ABSTRACT
Miscarriage is a major reproductive health crisis affecting 15% of all clinically confirmed pregnancies, and
recurrent pregnancy loss impacts 1-2% of women. Progesterone action through the progesterone receptor
in the uterus is essential for pregnancy establishment and maintenance, whereas dysregulated progesterone
signaling is associated with infertility and proinflammatory gynecological diseases. Differentiation of
endometrial stromal fibroblasts in the uterus, termed decidualization, is a key progesterone signaling-driven
process in early pregnancy that protects and nourishes the growing embryo before formation of the placenta.
For this purpose, decidualization normally suppresses inflammation, but both defective decidualization and
a hyperinflammatory uterine environment are associated with pregnancy loss. To better diagnose, treat, and
prevent recurrent pregnancy loss and proinflammatory gynecological diseases, a deeper understanding of
how the progesterone receptor works with other factors to regulate gene expression in individual uterine cell
types is needed. Serum response factor (SRF) plays important transcriptional roles in many tissue types and
has been suggested as a progesterone receptor regulator in the uterus. This proposal aims to elucidate
SRF's fundamental role in maintaining homeostatic uterine progesterone signaling for control of inflammation
and enabling of healthy decidualization. Aim 1 will Investigate SRF's function in defining in vivo uterine cell
composition and cell-specific gene regulation by first analyzing conditional Srf knockout mouse uteri over
time to identify the onset of SRF deficiency-driven uterine dysregulation and then using single cell resolution
RNA-sequencing and ATAC-sequencing combined with spatially resolved transcriptomics to reveal the cell
type-specific molecular mechanism of the uterine dysregulation. Aim 2 will reveal the mechanism of SRF-
dependent anti-inflammatory action in cultured human endometrial stromal cells (hESC) by first identifying
inflammatory pathways activated by SRF deficiency in hESC and then testing targeted innate immune
suppression to mitigate proinflammatory effects and restore normal decidualization. Overall, this research
will uncover how SRF regulates progesterone signaling in the uterus to prevent inflammation, fibrosis, and
decidualization failure. Studies on how SRF deficiency-driven inflammation leads to endometrial
inflammation and infertility will serve as a model for understanding the interplay between progesterone
signaling and inflammation with the goal of providing answers for recurrent miscarriage and proinflammatory
gynecological diseases.

## Key facts

- **NIH application ID:** 10933112
- **Project number:** 1FI2GM154603-01
- **Recipient organization:** U.S. NATIONAL INST OF ENVIRON HLTH SCIS
- **Principal Investigator:** Ryan Marquardt
- **Activity code:** FI2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2024-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10933112

## Citation

> US National Institutes of Health, RePORTER application 10933112, The Role of SRF in Uterine Homeostasis (1FI2GM154603-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10933112. Licensed CC0.

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