# Investigation of epigenetic and morphological placental abnormalities induced by in vitro fertilization

> **NIH NIH F32** · UNIVERSITY OF PENNSYLVANIA · 2020 · $25,634

## Abstract

Project Abstract
Several million babies worldwide have been born via Assisted Reproductive Technologies (ART). Although the
majority of ART pregnancies result in healthy babies, ART is associated with a number of adverse effects,
including increased risk for low birth weight, abnormal placental development, and rare imprinting disorders.
Evidence from animal studies support that ART procedures can induce these effects independent from
underlying infertility. Important for proper development and growth, imprinted genes are a unique subset of
genes that are monoallelically expressed specific to the parent-of-origin. Notably, imprinted gene expression is
regulated by DNA methylation at a discrete element known as the imprinting control region (ICR). Term
placentae from mice generated by in vitro fertilization (IVF) display abnormal biallelic expression correlated
with ICR hypomethylation for several imprinted genes. Additionally, IVF induces abnormal placental
overgrowth. The main objective of this proposal is to test how individual IVF procedures affect placental
function and to elucidate the underlying genetic and epigenetic mechanisms of this abnormal placentation.
Because the placenta has been shown to be capable of compensating for environmental perturbations, the
epigenetic and morphological changes observed may not result in physiological consequences. To address
this, formation, cell composition, pathology, and nutrient transport function of the placenta will be assessed in
natural, embryo transfer with and without superovulation, embryo culture, and IVF concepti in Aim 1. Because
different cell types have distinct epigenetic and expression profiles, several limitations currently exist making
molecular analyses of complex tissues, like the placenta, difficult. To remedy this, laser capture
microdissection (LCM) and single-molecule quantitative fluorescence in situ hybridization (FISH) will be
utilized. To determine gene expression changes that may be responsible for the abnormal placental
phenotype, transcriptome analyses will be performed in Aim 2 on ectoplacental cone and chorion (E7.5) and
junctional zone and labyrinth (E14.5) isolated by LCM from natural and IVF concepti. In Aim 3, gene
expression and single-molecule FISH methods will be employed to test the hypothesis that particular imprinted
genes play a role in the underlying mechanism resulting in IVF-induced placental overgrowth. Determining how
epigenetic changes influence placentation is important not only in the context of IVF, because the placenta is
critical for overall offspring and maternal health. Furthermore, the pipeline developed during this fellowship may
prove indispensible for future epigenetic investigations of other complex tissues.

## Key facts

- **NIH application ID:** 10268155
- **Project number:** 5F32HD089623-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Lisa Anne Vrooman
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $25,634
- **Award type:** 5
- **Project period:** 2017-08-01 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10268155

## Citation

> US National Institutes of Health, RePORTER application 10268155, Investigation of epigenetic and morphological placental abnormalities induced by in vitro fertilization (5F32HD089623-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10268155. Licensed CC0.

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