# Maternal obesogenic diet-induced changes in embryo and fetal DNA methylation programming

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $704,154

## Abstract

PROJECT SUMMARY
Obesity in reproductive-age women has sharply increased over the past few decades and is expected to continue
to rise for the foreseeable future. Besides a greater likelihood of pregnancy complications, such as preeclampsia
and preterm birth, obese women are also more likely to experience severe pregnancy outcomes, including
maternal death. In obese women undergoing infertility treatment, reports of poor/delayed ovarian stimulation, a
higher frequency of in vitro fertilization (IVF) failure, and defects in placentation suggest that obesity negatively
affects multiple reproductive processes, but the mechanisms remain largely unknown. Studying these events in
humans is difficult due to ethical and technical limitations, as well as the challenge of controlling for confounding
environmental factors. Through a National Centers for Translational Research in Reproduction and Infertility
(NCTRI) grant, a cohort of rhesus macaque females receiving either a low-fat control diet or a high-fat Western-
Style Diet (WSD) was established to study the adverse effects of obesity and diet on reproductive function.
Fertility trials conducted with these females demonstrated that WSD consumption delayed the time to pregnancy
and was associated with multiple placental abnormalities. Each female then underwent an IVF cycle to determine
the impact of maternal diet on preimplantation embryogenesis. Blastocyst formation was significantly reduced in
the WSD group and preliminary RNA-seq data from these blastocysts revealed altered expression of genes
involved in critical peri-implantation processes. Considering the important role of epigenetic modifications in
regulating gene expression changes during embryonic and fetal development, here we propose to investigate
how maternal WSD-induced metabolic dysfunction impairs developmental programming at the molecular level
and whether it can be reversed after resuming a low-fat diet. First, we will assess if there are alterations in DNA
methylation, gene expression, and/or chromosome fidelity in preimplantation embryos from female macaques
with increased adiposity and insulin resistance induced by WSD exposure. By examining changes that persist
after a short versus long-term diet reversal, we will also determine whether it is a dietary intervention or overt
weight loss that can improve IVF outcomes (Aim 1). Secondly, we will utilize the fetal thymus, spleen, liver, and
kidney collected from low-fat diet and WSD-fed mothers during the NCTRI fertility trial to determine how maternal
diet and metabolism influences DNA methylation and gene expression across fetal tissues. Comparing these
results to the placenta, as well as maternal and cord blood, from the same subjects will help identify epigenetic
signatures that are trans-generationally shared versus fetus-specific (Aim 2). Further comparison of DNA
methylation and gene expression between embryos and fetuses will reveal genomic regions that are not only
important f...

## Key facts

- **NIH application ID:** 10981884
- **Project number:** 1R01HD113689-01A1
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Lucia Carbone
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $704,154
- **Award type:** 1
- **Project period:** 2024-09-13 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10981884

## Citation

> US National Institutes of Health, RePORTER application 10981884, Maternal obesogenic diet-induced changes in embryo and fetal DNA methylation programming (1R01HD113689-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10981884. Licensed CC0.

---

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