# Pathways Affecting Trophoblast Development

> **NIH NIH R01** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2024 · $633,680

## Abstract

PROJECT SUMMARY/ABSTRACT
Trophoblast cell derivatives of the early embryo contribute to restructuring the uterine environment, an event
required for the establishment of a successful pregnancy. The human and rat each possess a uterine-
trophoblast interface that is characterized by deep intrauterine infiltration of trophoblast cells, which contributes
to dynamic changes in uterine immune cell, endothelial cell, smooth muscle cell, and stromal cell constituents.
This important developmental process is directed by specialized trophoblast cells possessing invasive
properties referred extravillous trophoblast (EVT) in the human or by the generic term invasive trophoblast cells
in other species, including the rat. Differentiation into these specialized trophoblast cell types requires
suppression of pathways essential for maintaining the trophoblast cell stem state and activation of the
invasive/EVT cell differentiation program. We hypothesize that repression of the trophoblast cell stem state is
an event essential for the establishment of pregnancy. In this project, we investigate roles for activin-follistatin
like 3 and WNT-WNT antagonist regulatory networks controlling development of the invasive/EVT cell lineage.
Roles for the activin-follistatin like 3 and WNT-WNT antagonist regulatory networks are the focus of Aims Nos.
1 and 2, respectively. In Aim No. 3, we examine FSTL3 and the WNT antagonist, NOTUM, in patient-specific
human trophoblast stem cells. Experimentation includes genome-wide analyses of the transcriptome and the
chromatin landscape. Execution of this research project will facilitate elucidation of elements of the regulation
of the invasive/EVT cell lineage and will create a platform for understanding the pathogenesis of early
pregnancy loss.

## Key facts

- **NIH application ID:** 10905500
- **Project number:** 1R01HD112559-01A1
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** MICHAEL J SOARES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $633,680
- **Award type:** 1
- **Project period:** 2024-06-13 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10905500

## Citation

> US National Institutes of Health, RePORTER application 10905500, Pathways Affecting Trophoblast Development (1R01HD112559-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10905500. Licensed CC0.

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