# Stress-mediated trophoblast proliferation: adaptation or pathology?

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $334,688

## Abstract

Project Summary/Abstract
For many pregnancies, there are few effective ways to treat placental diseases that result in fetal demise, poor
fetal outcome and/or increased risk of fetal programing of adult onset disease. Poor placental function is a
contributing cause of pregnancy related diseases, including intrauterine growth restriction (IUGR) and
preeclampsia (PE). Despite decades of research investigating pregnancy and fetal outcome, there is no true
understanding of how the basic biological processes involved in placental development fail. Aberrant trophoblast
cell proliferation and differentiation have been considered responsible, however the etiology is not understood
and in many cases, obstetricians can only manage the mothers' symptoms. Although persistent proliferation of
trophoblast cells occurs throughout gestation in both the human and mouse placentae, human Trophoblast Stem
(TS) cells, which have just recently been identified, are not thought to persist beyond early development. This
leaves a gap in our understanding of the mechanisms that support placental homeostasis and regenerative
potential, later in pregnancy. Mouse TS cells, on the other hand, are better characterized. They have been used
as an investigational model of the molecular mechanisms supporting trophoblast proliferation and differentiation,
thereby contributing to our understanding of placental development and function, though they are thought to be
depleted by E8.5 of a 20-day gestation. In many organs, tissue-specific stem/progenitor cells underlie
homeostasis and provide an ability to adapt to stress and injury. Characterizing human TS cells could offer the
8-10% of pregnancies that encounter complications hope through regenerative medicine. Applying this logic, our
lab identified increased trophoblast proliferation and expression of the TS marker, Eomes, beyond early
development and have found a population of proliferative, multipotent TS-like cells using Sca-1 as a cell surface
marker, in the late gestation mouse placenta. Our governing hypothesis is that placental stress confers
proliferative potential to a sub-population of trophoblast, and we propose this population is critical to fetal health.
The objectives of this proposal are to use cutting edge genetic and genomic techniques to study persistent TS
and Sca-1+ trophoblast populations in the context of placental insufficiency and assess whether they provide the
mouse placenta an adaptive mechanism. We will investigate the function of Sca-1(Ly6A) in mouse trophoblast
to provide insight into the adaptive response. Additionally, we will compare the transcriptomes of mouse TS to
the novel human TS cells, focusing on transcription factors and cell surface markers to define specific
subpopulations to then evaluate the adaptive response of the human placenta. Ultimately, our work will
determine the regenerative capacity of the placenta and aid in identifying the role human TS cells in this process,
to develop new t...

## Key facts

- **NIH application ID:** 9980451
- **Project number:** 5R01HD100179-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** LOUISE CHANG LAURENT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $334,688
- **Award type:** 5
- **Project period:** 2019-07-20 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980451

## Citation

> US National Institutes of Health, RePORTER application 9980451, Stress-mediated trophoblast proliferation: adaptation or pathology? (5R01HD100179-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9980451. Licensed CC0.

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