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

> **NIH NIH P50** · UNIVERSITY OF PENNSYLVANIA · 2024 · $472,659

## Abstract

Project Summary
Since the advent of in vitro fertilization over 40 years ago, over 8 million children have been born using these
assisted reproductive technologies (ART). New procedures and interventions are continuously being developed
to improve efficiency, safety, and success while allowing for greater options for patients desiring fertility, now
and in the future. ART has been associated with increased risk of adverse perinatal outcomes and markers of
future cardiometabolic disease in some offspring. Investigation of specific interventions, including emerging
technologies such as oocyte vitrification, is critical to understanding the mechanisms of these potential short-
and long-term health effects. Importantly, the majority of children born from IVF are under the age of 30, therefore
the long-term consequences of conception with ART across the lifespan remain to be seen. Furthermore, ART
is constantly evolving with new technologies being rapidly incorporated into routine clinical care without long-
term follow-up data yet available. The vast majority of pregnancies following ART are healthy; however, our prior
studies have demonstrated some of these individuals have disrupted epigenomes; these disruptions are
associated with clinical phenotypes (e.g. low birth weight) and these epigenetic signatures vary by specific ART
intervention (e.g. fresh vs frozen embryo transfers). We hypothesize that ART pregnancies with the greatest
epigenetic disruption will be more likely to have adverse perinatal outcomes and be more likely to exhibit
cardiometabolic changes during childhood, and that these disruptions will vary based on specific ART
interventions. In Specific Aim 1 we will investigate the effect of oocyte vitrification on epigenomic perturbations
in DNA methylation in both embryonic (cord blood) and placental tissues and examine the effect of maternal age
on these epigenetic changes. In Aim 2 we will determine whether 1) a disrupted placental epigenome or 2) cell
free fetal DNA fraction, are associated with ART interventions and if these markers can identify patients with
adverse perinatal outcomes. In Aim 3 we will determine whether perturbations in DNA methylation at birth persist
into childhood and are associated with adverse metabolic parameters and/or abnormal female reproductive
function in childhood. This proposal continues our work examining individual ART interventions to identify those
that lead to the greatest perturbations in the epigenome, and additionally, those that may potentially lead to
adverse outcomes both in pregnancy and into adulthood. Though restrictions on human embryo research
prevent us from mechanistic studies in humans, our parallel aims in Project 2 will allow us to further investigate
the mechanisms involved in ART-associated adverse outcomes in a mouse model. In addition, our work in
Project 3, will further investigate the role of sex in ART outcomes using innovative in vitro models to study early
placentation. I...

## Key facts

- **NIH application ID:** 10992941
- **Project number:** 2P50HD068157-11A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Suneeta Senapati
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $472,659
- **Award type:** 2
- **Project period:** 2011-05-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10992941

## Citation

> US National Institutes of Health, RePORTER application 10992941, Project 1: Epigenetic Regulation of Placental and Fetal Gene Expression in Human Pregnancy (2P50HD068157-11A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10992941. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*