# Project 2: Epigenetic, Behavioral, and Physiological Outcomes in a Mouse ART Model

> **NIH NIH P50** · UNIVERSITY OF PENNSYLVANIA · 2022 · $384,909

## Abstract

Abstract
Assisted Reproductive Technologies (ART) are invaluable for the increasing number of
women who require interventions to treat their infertility. Nevertheless, ART-conceived
children are at increased risk for loss-of-imprinting disorders resulting from epigenetic
errors, abnormal growth, congenital malformations, and postnatal cardiac and metabolic
disorders. Such problems likely arise because ART procedures take place when the
mammalian embryo is being epigenetically reprogrammed. Because it is difficult to
conduct studies using human embryos, a mouse model system, which anticipated some
risks associated with ART, will be used to assess the effect of ART interventions on
placental morphology, imprinted gene regulation, growth, metabolic and cardiac
phenotypes of the offspring, and epigenetic gene regulation, including DNA methylation
and chromatin structure genome-wide. Presently, preliminary evidence suggests that
frozen embryos transferred into unstimulated women have less perinatal morbidity than
fresh cycles but conflicting data suggest adverse outcomes associated with frozen
embryos. Specific Aim 1 will determine the effects of embryo vitrification and maternal
hormonal environment on offspring outcome of IVF-generated embryos. Moreover,
preimplantation genetic screening (PGS) is being increasingly employed in the absence
of research assessing the consequences of blastomere biopsy. Specific Aim 2 will
investigate the phenotypes and epigenetic profiles of the placenta and ART offspring
derived when PGS is used. Finally, data from our human placental studies demonstrate
alterations in DNA methylation in genes critical to early placentation, fetal growth, and
adult metabolism. Specific Aim 3 will translate these data to our animal ART model to
determine the role of specific genes in adverse outcomes associated with IVF. The role
of Grb10 in IVF-associated changes in fetal growth, placentation, and vasculogenesis
using a mouse model will be initially assessed. Results of these experiments will provide
information regarding the linkage between epigenetic changes and health of offspring
conceived by ART. These findings may also suggest experimental modifications to ART
procedures that can improve offspring outcomes.

## Key facts

- **NIH application ID:** 10372962
- **Project number:** 5P50HD068157-10
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** MARISA S. BARTOLOMEI
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $384,909
- **Award type:** 5
- **Project period:** 2011-05-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10372962

## Citation

> US National Institutes of Health, RePORTER application 10372962, Project 2: Epigenetic, Behavioral, and Physiological Outcomes in a Mouse ART Model (5P50HD068157-10). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10372962. Licensed CC0.

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