# Perfluroalkylated Substances Exposures and Cytotrophoblast Differentiation

> **NIH NIH K99** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $91,867

## Abstract

Project Summary/Abstract.
 The goal of this project is to test the hypothesis that perfluoroalkylated substances (PFAS) negatively
impact formation of the placenta, and consequently, pregnancy outcomes. This work gains added significance
in light of the increasing public health concerns towards these persistent compounds. The proposed
experiments will also fill gaps in our understanding regarding the effects of these chemicals during human
placental development, about which little is known. Pregnant mothers are exposed to a variety of chemicals,
including PFAS. The latter exposures are widespread and high levels are linked with adverse effects on thyroid
function, cholesterol metabolism, and birth outcomes. The placenta, a temporary embryonic/fetal organ that
forms during pregnancy, facilitates gas, nutrients, and waste exchange with the mother. Deficiencies in
placental development and function underlie numerous pregnancy complications, such as preeclampsia and
intrauterine growth restriction. Despite its importance much remains unknown about the placenta, especially its
role as a toxicological target. Here I propose studying PFAS effects on the organ's population of progenitor
cells, termed cytotrophoblasts (CTBs), which establish the architecture of the maternal-fetal interface during
pregnancy. To do so I will use an in vitro model of this process. Primary CTBs will be isolated and exposed to
PFOA, PFNA, or GenX. The toxicological effects of these PFAS will be elucidated in two ways. First, using the
CTB model, relevant effective concentrations of PFOA, PFNA, or GenX will be determined and a mass
spectrometry-based approach will be used to determine their global effects at the level of the proteome (Aim
1). Second, honing in on levels relevant to public health exposures, the functional relevance of PFAS protein
targets that could play hierarchical roles in placental development will be investigated by mimicking the
observed chemical effects, e.g., up or down regulation (Aim 2). Thus, the results of these experiments will
advance our knowledge about the human health effects of the compounds during a critical developmental
window. Completing this study will advance the applicant's training in important new directions that are enabled
by the expertise of his primary mentor, Dr. Susan Fisher: human placental biology and mass spectrometry-
based proteomics analyses. Dr. Hao Chen will receive valuable input from his mentorship team, composed of
experts in prenatal environmental exposures, bioinformatics, and reproductive biology. In collaboration with his
mentors, Dr. Chen will develop critical skills that are required for a successful transition to an independent
academic career in environmental health. This will be accomplished through a focused development plan
consisting of didactic courses and close collaboration with his mentors. At the conclusion of this proposal, Dr.
Chen will have led the first investigation of PFAS effects on CTBs and the...

## Key facts

- **NIH application ID:** 9892276
- **Project number:** 1K99ES030401-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Hao Chen
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $91,867
- **Award type:** 1
- **Project period:** 2020-01-15 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9892276

## Citation

> US National Institutes of Health, RePORTER application 9892276, Perfluroalkylated Substances Exposures and Cytotrophoblast Differentiation (1K99ES030401-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9892276. Licensed CC0.

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