# Molecular and bioenergetic dynamics of in utero chronic hypoxia on placenta and brain

> **NIH NIH R21** · CHILDREN'S HOSP OF PHILADELPHIA · 2024 · $260,887

## Abstract

PROJECT SUMMARY
Insufficiency of the placenta due to conditions such as hypertension, diabetes, and fetal congenital heart
disease can lead to chronic in utero hypoxia. Chronic hypoxia increases the risk of neurodevelopmental
disorders by disrupting the "placenta-brain" axis. Furthermore, the effects of chronic hypoxia on the developing
brain include disrupted energy metabolism and epigenome disruption, also called the metabolic-epigenetic
axis. Rodent models of prenatal hypoxia are useful for studying the complex relationship between the placenta,
brain, and epigenome.
We developed 4D in utero Oxy-wavelet MRI (4D-uMRI) technology for simultaneous structural and temporal
mitochondrial dynamics assessment. We applied this technique to elucidate the variable metabolic dynamics of
multiple models of prenatal injury. We have additional expertise in modeling prenatal brain injury and analyzing
the effects of injury on the molecular phenotype of the developing brain through single nucleus multi-omics.
In this proposal, we will leverage our combined expertise to study the effects of chronic hypoxia on the
placenta, brain, and epigenome. Our team has expertise in neuroscience, imaging, pathology, and placental
biology. This study allows us to derive a comprehensive understanding of the correlation between metabolic
profiling and molecular phenotype. We will compare normoxic litters to animals exposed to 11% inspired
oxygen from embryonic day 14.5 to 17.5. In Aim 1, we will use 4D-uMRI studies to determine to examine the
relationship between placental structural anomalies and brain structural and metabolic dysfunction from
chronic hypoxia. The study will provide insight into whether there is a direct relationship between the extent of
placental insufficiency and brain metabolic disruption and growth parameters. In Aim 2, we will assess the
brain's metabolic response to hypoxia to test the relationship between the extent of metabolic dysfunction and
disruption of the transcriptome and epigenome through single nucleus multi-omic sequencing. The study
proposes an innovative approach to testing the correlation between the extent of metabolic disruption and
molecular phenotype. Together, these experiments will allow us to recognize novel correlations between
structure, function, and molecular disruption to discover novel targets for treating the neurodevelopmental
deficits from chronic hypoxic brain injury.

## Key facts

- **NIH application ID:** 10988582
- **Project number:** 1R21HD114071-01A1
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Ana Cristancho
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $260,887
- **Award type:** 1
- **Project period:** 2024-08-09 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10988582

## Citation

> US National Institutes of Health, RePORTER application 10988582, Molecular and bioenergetic dynamics of in utero chronic hypoxia on placenta and brain (1R21HD114071-01A1). Retrieved via AI Analytics 2026-06-13 from https://api.ai-analytics.org/grant/nih/10988582. Licensed CC0.

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