# THE ROLE OF MESENCHYMAL PROGENITOR CELLS IN ABNORMAL UTERINE REPAIR

> **NIH NIH R01** · YALE UNIVERSITY · 2024 · $42,192

## Abstract

PROJECT SUMMARY
Dilation & curettage (D&C) is one of the most common surgical procedures performed on women throughout
the world. Intrauterine adhesions (iUA), or Asherman, develop in about 40% of women who undergo D&C in
the postpartum (6 week period after birth), but is very rare after D&C in nonpregnant women (<1%) for reasons
that are not well understood. It is a debilitating condition characterized by intrauterine fibrosis and scarring.
Patients with iUA suffer from infertility, recurrent pregnancy loss and a broad range of dangerous pregnancy
complications (e.g. preterm birth). While endometrial mesenchymal stem/progenitor cells (eMPCs) and
macrophage immune cell populations are crucial for endometrial repair and postpartum uterine remodeling, the
role of these cells and underlying molecular mechanisms in this postpartum susceptibility of the endometrium
to fibrosis and abnormal repair are unknown. This application is specifically focused on defining the role that
macrophages play in abnormal uterine repair, given the known important role of macrophage activation as a
driver of fibrosis in other organs. The central hypothesis is that macrophages in the postpartum uterus are
polarized to M2 phenotype, resulting in a profibrotic response to uterine injury as compared to M1
macrophages of the nonpregnant uterus, ultimately leading to fibrosis and scar formation. The approach is to
use our novel postpartum mouse uterine injury model which recapitulates the susceptibility of the human
postpartum uterus to injury. Using this model, we will characterize the macrophage populations and
polarization dynamics in the postpartum and nonpregnant uterus in response to injury (Aim 1). We will directly
examine the role of macrophage polarization in inducing profibrotic transformation of endometrial stromal
fibroblasts using in vitro co-cultures (Aim 2) to gain detailed insights into the cellular and molecular differences
that predispose the postpartum endometrium to form iUA. The proposed aims are conceptually innovative and
together will have a broad impact on the field by filling a substantial gap in our fundamental knowledge of
endometrial biology and infertility pathogenesis. Ultimately, the knowledge gained from this proposal will not
only be invaluable to our understanding of many more subtle conditions of abnormal endometrial repair, but
provide unique insights into the body’s physiological anti-fibrotic wound healing mechanisms leading to a
deeper understanding of the pathogenesis of fatal idiopathic fibrotic diseases in other organs.

## Key facts

- **NIH application ID:** 10930393
- **Project number:** 3R01HD109326-01A1S1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Reshef Tal
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $42,192
- **Award type:** 3
- **Project period:** 2023-05-15 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10930393

## Citation

> US National Institutes of Health, RePORTER application 10930393, THE ROLE OF MESENCHYMAL PROGENITOR CELLS IN ABNORMAL UTERINE REPAIR (3R01HD109326-01A1S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10930393. Licensed CC0.

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