# TGF-BETA SIGNALING IN ENDOMETRIAL CELL FUNCTION AND DYSFUNCTION

> **NIH NIH R01** · TEXAS A&M AGRILIFE RESEARCH · 2021 · $297,669

## Abstract

Title:
TGF-BETA SIGNALING IN ENDOMETRIAL CELL FUNCTION AND DYSFUNCTION
Project Summary/Abstract
An increasing number of reproductive-aged women face pregnancy loss and infertility, some of which is
associated with endometrial dysfunction. A lack of understanding of mechanisms governing endometrial
development and function prevents an effective treatment for such disorders. Therefore, there is a critical
need to define the mechanisms underlying endometrial cell proliferation, differentiation, and function.
Research on human endometrial function during pregnancy remains challenging due to ethical constrains on
the access to tissue specimens, making the mouse model particularly valuable. Transforming growth factor β
(TGFβ) superfamily signaling regulates fundamental cellular functions and developmental processes in
reproductive organs including the uterus. The in vivo function of TGFβ signaling in uterine biology remains
poorly understood due to the redundancy of TGFβ ligands and lack of appropriate animal models. By
genetically manipulating TGFβ type 1 receptor (TGFBR1) using both loss-of-function and gain-of-function
mouse models, we have discovered that TGFβ signaling is required for fertility and female reproductive tract
development. Guided by our compelling preliminary findings, the overall objective in this R01 proposal is to
decipher the cellular, molecular, and epigenetic mechanisms underpinning endometrial cell proliferation,
differentiation, and function. Our central hypothesis is that endometrial cell properties and function are
regulated by a well-balanced TGFβ signaling system essential for uterine development and pregnancy. We
will test our hypothesis by pursuing the following two specific aims: 1) Define how TGFβ signaling regulates
endometrial epithelial cell proliferation during uterine development. 2) Identify the role and associated
mechanism of TGFβ signaling in endometrial stromal cell function and dysfunction during pregnancy. The
proposed research is innovative because it involves the use of unique and complementary novel mouse
models to decipher the role and associated mechanisms of TGFβ signaling in endometrial cells, the
application of uterine epithelial and stromal cell culture and co-culture system to uncover how
TGFβ signaling regulates stromal-epithelial interaction, a key but poorly defined event in uterine development
and function, and the identification of TGFBR1-dependent epigenetic mechanisms in endometrial stromal
cells. Studies proposed in this application represent the next step in a continuum of research toward the
development of targeted interventions for endometrial dysfunction and pregnancy complications. Thus,
completion of this proposal is expected to provide a new paradigm for understanding the mechanisms of
endometrial dysfunction, and provide a rational basis for future research that focuses on testing the
translational potential of targeting TGFβ signaling cascade in the treatment of endometrial dysfu...

## Key facts

- **NIH application ID:** 10112273
- **Project number:** 5R01HD087236-05
- **Recipient organization:** TEXAS A&M AGRILIFE RESEARCH
- **Principal Investigator:** Qinglei Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $297,669
- **Award type:** 5
- **Project period:** 2017-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10112273

## Citation

> US National Institutes of Health, RePORTER application 10112273, TGF-BETA SIGNALING IN ENDOMETRIAL CELL FUNCTION AND DYSFUNCTION (5R01HD087236-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10112273. Licensed CC0.

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