# Project 1: Epigenetic Regulation of Placental and Fetal Gene Expression in Human Pregnancy

> **NIH NIH P50** · UNIVERSITY OF PENNSYLVANIA · 2021 · $481,802

## Abstract

Project Summary
A fundamental question relevant to clinical IVF is whether and how the peri-conceptional milieu
affects embryo implantation and placentation and how clinical manipulations of this environment
influence perinatal outcomes. Changes in trophoblast differentiation and function, perturbations of
placental vascular development and/or sub-optimal endometrial regeneration during clinical or
laboratory manipulations such as trophectoderm biopsy could all contribute to abnormal implantation
and placentation and lead to an abnormal fetal growth phenotype. We hypothesize that epigenetic
changes in specific placental cellular compartments (embryonic or extraembryonic) and/or the
endometrium contribute to the significant adverse outcomes associated with IVF and, specifically,
following fresh (hyperstimulated) vs. frozen/thawed embryo transfer or natural conception or following
trophectoderm biosy. We suggest that these epigenetic alterations lead to abnormal gene expression
at critical times during development, implantation and placentation and result in abnormal growth and
other complications. In Specific Aim 1A we will identify site- and gene-specific epigenetic differences
in placentas, in isolated trophoblasts, placental vasculature and endothelial cells from pregnancies
following fresh/hyperstimulated vs. frozen/thawed vs. control pregnancies. In Specific Aim 1C, we will
begin exploring whether there is an endometrial contribution to the observed peri-conceptional milieu
growth-related differences as well. In Specific Aim 2 we will identify specific epigenetic differences in
placentas and in isolated trophoblast cells, placental vasculature and endothelial cells in pregnancies
following trophectoderm biopsy. In this "clinical" project, we focus on identifying the epigenetic
signature(s) related to abnormal placental function and an abnormal birth weight phenotype. In
Specific Aim 3 we will determine whether the epigenetic signature determined at birth persists into
childhood and may be associated with long term health consequences such as obesity. This initiative
continues to be discovery-driven, has and will continue to inform mechanistic studies for our mouse
model (Project 2) and should contribute to our understanding of optimal human embryo development,
implantation and placentation.

## Key facts

- **NIH application ID:** 10133693
- **Project number:** 5P50HD068157-09
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** CHRISTOS COUTIFARIS
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $481,802
- **Award type:** 5
- **Project period:** 2011-05-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133693

## Citation

> US National Institutes of Health, RePORTER application 10133693, Project 1: Epigenetic Regulation of Placental and Fetal Gene Expression in Human Pregnancy (5P50HD068157-09). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10133693. Licensed CC0.

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