# Trophoblast Differentiation

> **NIH NIH R01** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2020 · $471,973

## 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. Disruptions in this fundamental
process lead to diseases of pregnancy and placentation, and result in impaired nutrient transport to the fetus,
including the delivery of oxygen. Hypoxemia leads to a range of disruptive events within the fetus that have
potentially long-lasting postnatal impacts on health and disease. Mechanisms controlling uterine spiral artery
remodeling remain poorly understood. Central to the vascular remodeling process is a specialized population
of trophoblast cells referred to as invasive trophoblast or alternatively as extravillous trophoblast. Regulatory
processes controlling differentiation and function of the extravillous trophoblast cell lineage is the focus of this
proposal. The rat is used as an experimental model in this investigation because it exhibits deep intrauterine
trophoblast invasion and extensive uterine spiral artery remodeling. These events are remarkably similar to that
observed in human placentation. The experimental effort is based on our prior establishment and extensive
characterization of in vitro and in vivo models for studying rat hemochorial placentation. Through these efforts
we discovered key regulators that promote development of the invasive trophoblast lineage: i) Fos like antigen
1/JunB protooncogene; ii) hypoxia/hypoxia inducible factor/lysine demethylase 3A/matrix metalloproteinase 12.
These regulators contribute to establishing tissue plasticity and safeguard placental health. Most importantly,
we have determined that plasticity is a hallmark of a healthy placenta. In this proposal we utilize FOS Like
Antigen 1/JunB protooncogene and hypoxia/hypoxia inducible factor/ lysine demethylase 3A/matrix
metalloproteinase 12 regulatory circuits as centerpieces and guides to mechanisms controlling the development
of the extravillous trophoblast lineage. The proposed research provides an innovative approach to studying
hemochorial placentation. Collectively, the research is directed toward elucidating molecular mechanisms
underlying physiological processes that ensure appropriate hemochorial placentation. This approach will lead to
the identification of conserved regulatory pathways controlling the extravillous trophoblast lineage, which will
create opportunities for new scientific and applied pursuits.

## Key facts

- **NIH application ID:** 9922124
- **Project number:** 5R01HD020676-32
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** MICHAEL J SOARES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $471,973
- **Award type:** 5
- **Project period:** 1986-07-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9922124

## Citation

> US National Institutes of Health, RePORTER application 9922124, Trophoblast Differentiation (5R01HD020676-32). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9922124. Licensed CC0.

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