# Anti-Coagulation Factors and Placentation

> **NIH NIH R01** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2022 · $496,687

## Abstract

PROJECT SUMMARY/ABSTRACT
Hemochorial placentation occurs in many mammalian species including primates and rodents. It ensures the
most intimate contact between maternal and embryonic compartments and requires specialized adjustments.
Among these adjustments is the need for extensive remodeling of the maternal uterine spiral arteries. Uterine
vascular modifications are required for the delivery of nutrients to the fetus. Central to the vascular remodeling
process is a specialized population of trophoblast cells referred to as invasive trophoblast cells and in the
human, extravillous trophoblast. These cells migrate from the placenta into the uterus where they contribute to
the restructuring of the uterine spiral arteries, which facilitate the delivery of nutrients to the placenta and fetus.
Disruptions in this fundamental process lead to diseases of pregnancy and placentation, including the “Great
Obstetrical Syndromes” (preeclampsia, intrauterine growth restriction, preterm birth, abruptio placentae). Many
of these disorders are associated with coagulopathies. In this research proposal we investigate roles for two
anti-coagulation factors, tissue factor pathway inhibitor (TFPI) and thrombomodulin (THBD), as a regulators of
invasive trophoblast lineage development and uterine spiral artery remodeling. Our proposed research uses
the rat as an experimental model because it exhibits deep intrauterine trophoblast invasion and extensive
uterine spiral artery remodeling similar to human placentation. We will utilize rat and human trophoblast stem
cells to evaluate molecular mechanisms involved in differentiation of the invasive trophoblast lineage.
Hypotheses for the conserved involvement of TFPI and THBD in placentation will be tested in vivo using rat
models created by genome editing and through lentiviral-mediated trophectoderm gene manipulation. This
study will facilitate elucidation of molecular pathways controlling the invasive trophoblast cell lineage and
uterine spiral artery remodeling and create a platform for understanding the pathogenesis of diseases
impacting placentation.

## Key facts

- **NIH application ID:** 10403684
- **Project number:** 5R01HD099638-04
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** MICHAEL J SOARES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $496,687
- **Award type:** 5
- **Project period:** 2019-07-17 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10403684

## Citation

> US National Institutes of Health, RePORTER application 10403684, Anti-Coagulation Factors and Placentation (5R01HD099638-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10403684. Licensed CC0.

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