# A new animal model for investigating the invasive trophoblast lineage

> **NIH NIH R21** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2022 · $238,959

## Abstract

PROJECT SUMMARY/ABSTRACT
The placenta plays a crucial role during pregnancy ensuring fetal growth and development. Successful
pregnancy hinges upon placental adaptations to the maternal environment. The human placenta is classified as
hemochorial and is characterized by extensive intrauterine trophoblast cell invasion. During the course of the
gestation, invasive trophoblast cells or extravillous trophoblast, as they are referred to in humans, migrate from
the placenta into the uterine parenchyma where they act to anchor the placenta to the uterus and remodel uterine
spiral arteries. Uterine vascular remodeling is central to providing adequate nutrient flow to the fetus and normal
fetal development. Abnormalities in the organization and structure of trophoblast cell populations are associated
with pregnancy disease states. Shallow trophoblast invasion and aberrant modification of the uterine vasculature
are directly linked to preeclampsia, early pregnancy loss, intrauterine growth restriction, pre-term birth, and
placental abruption. On the other hand, excessive trophoblast invasion, as in disorders such as placenta accreta,
jeopardizes pregnancy, maternal health, and future-child bearing. Molecular events that trigger the differentiation
of invasive trophoblast cell lineages and trophoblast-guided uterine spiral artery remodeling are poorly
understood. Experimental tools are in-hand to identify candidate regulators of the invasive trophoblast cell
lineage and to test their physiological relevance. Placentation in the rat is characterized by extensive intrauterine
trophoblast invasion and trophoblast-guided spiral artery remodeling resembling developmental processes
evident in human placentation. Global genome-editing in the rat is an effective tool for investigating a sub-set of
candidate genes implicated in regulating deep placentation but not all candidate genes regulating deep
placentation. Some genes possess multiple roles in embryogenesis, precluding an evaluation of a specific role
in the invasive trophoblast cell lineage. The generation of a conditional allele circumvents this issue. In the
proposed research, we will generate a rat model for generating invasive trophoblast-lineage specific conditional
alleles using Crispr/Cas9 genome editing. In this project, we generate a transgenic rat model expressing Cre
recombinase in invasive trophoblast cells under control of Prl7b1 regulatory sequences and validate the Prl7b1-
Cre driver rat strain. The proposed experiments will provide valuable new tools for the scientific community to
discern roles for candidate genes in the regulation of trophoblast invasion and trophoblast-guided uterine spiral
artery remodeling, and thus a novel experimental paradigm to explore the etiology of high-risk pregnancies.

## Key facts

- **NIH application ID:** 10448294
- **Project number:** 5R21HD104071-02
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** Khursheed Iqbal
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $238,959
- **Award type:** 5
- **Project period:** 2021-07-10 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10448294

## Citation

> US National Institutes of Health, RePORTER application 10448294, A new animal model for investigating the invasive trophoblast lineage (5R21HD104071-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10448294. Licensed CC0.

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