# Long-term physiological and behavioral outcomes, epigenetic profiles and multigenerational phenotypes in a mouse ART model

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $327,393

## Abstract

Abstract
Infertile couples are increasingly turning to Assisted Reproductive Technologies (ART) to treat
their infertility. Of growing concern is that ART-conceived children are at increased risk for
specific loss-of-imprinting disorders, congenital malformations, growth restriction, preeclampsia
as well as postnatal cardiac and metabolic disorders. Given the difficulty of conducting studies
using human embryos, a mouse model system, which anticipated some risks associated with
ART, will be used to assess the effects of ART on placental morphology, imprinted gene
regulation, growth, metabolic, cardiac and behavioral phenotypes of the offspring, and gene
expression and chromatin structure genome-wide. Specific Aim 1 will assess the phenotypes,
including growth, behavior metabolism and cardiovascular function, of ART-offspring in
comparison to naturally-conceived controls. We will also interrogate imprinted gene regulation
and gene expression, DNA methylation and chromatin structure using gene-specific and high
throughput analyses. Moreover, the design of this aim will enable us to isolate, phenotype and
match placenta to offspring to determine whether the placental phenotype can accurately
predict health of in vitro fertilization (IVF)-derived offspring. Because we have previously
reported a low frequency of epigenetic errors in multiple tissues of IVF-conceived offspring, we
hypothesize that the germline cells also harbor epigenetic mutations. In Specific Aim 2, we will
test this hypothesis by determining whether aberrant phenotypes observed in IVF offspring are
transmitted to subsequent generations and, if so, assess the mechanism of this transmission.
The result from these experiments will provide a trove of information regarding the linkage
between epigenetic changes and health of offspring conceived by ART and whether placental
phenotyping can predict offspring health. Our findings may also suggest experimental
modifications to ART procedures that can improve offspring outcomes.
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## Key facts

- **NIH application ID:** 10152633
- **Project number:** 5R01HD092266-05
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** MARISA S. BARTOLOMEI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $327,393
- **Award type:** 5
- **Project period:** 2017-08-15 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10152633

## Citation

> US National Institutes of Health, RePORTER application 10152633, Long-term physiological and behavioral outcomes, epigenetic profiles and multigenerational phenotypes in a mouse ART model (5R01HD092266-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10152633. Licensed CC0.

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