# Impact of Prenatal Hypoxia on Mitochondrial Function of Offspring Hearts

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2021 · $529,212

## Abstract

Project Summary
Adverse events occurring during fetal life can contribute to an increased risk of disease in adult life. Chronic intrauterine
hypoxia causes fetal growth restriction and renders the offspring vulnerable to hypertension and heart disease as well as
other complications. Thus, the developmental origins of health and disease (DOHaD) hypothesis has posited a critical
role of prenatal care in etiologies of several disease conditions. Prenatal hypoxia has been shown to disrupt
cardiovascular function through mechanisms associated with both heart and blood vessel pathologies. We have generated
a well established hypoxic pregnant guinea pig model that exhibits fetal and offspring phenotype of mitochondrial
dysfunction. Further, our data show that exposure to hypoxia during the fetal growth phase inhibits contractile function in
the offspring heart. We propose that mitochondrial-specific mechanisms associated with biogenesis and bioenergetics in
the fetal heart are inhibited, which is sustained in the offspring and manifest as cardiac ventricular dysfunction. We will
determine the effects of prenatal hypoxia on mRNA/gene expression of the PGC1a/PPAR pathway and respiratory chain
complex expression in fetal hearts. We will evaluate the sustained consequences of prenatal hypoxia on mitochondrial
respiration in intact cardiac cells. Using live cell imaging with super-resolution confocal microscopy, we will identify the
effects of prenatal hypoxia on mitochondrial structure, membrane integrity, and Ca2+ transients in cell contraction of
cardiac cells from offspring hearts. We will evaluate ventricular dysfunction in the offspring hearts exposed to prenatal
hypoxia by echocardiography and pressure-volume loop analysis. Finally, we will treat pregnant sows and neonates with
nicotinamide modulators (resveratrol and nicotinamide riboside) to enhance the NAD+/NADH ratio, which is a central
regulator of energy metabolism. We will determine whether treatment enhances mitochondrial function and/or contractile
function of the offspring as a pharmacological approach for improving mitochondrial health and reducing the risk of heart
disease.

## Key facts

- **NIH application ID:** 10218255
- **Project number:** 5R01HL126859-07
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** LOREN P THOMPSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $529,212
- **Award type:** 5
- **Project period:** 2015-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10218255

## Citation

> US National Institutes of Health, RePORTER application 10218255, Impact of Prenatal Hypoxia on Mitochondrial Function of Offspring Hearts (5R01HL126859-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10218255. Licensed CC0.

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