top of page

How does Postnatal Diet Affect the Cardiac Outcome in Offspring from Hypoxic Pregnancies

Poor postnatal diet

A lack of oxygen to the developing fetus (prenatal hypoxia) is a common occurrence in complicated pregnancies.  Adult offspring from hypoxic pregnancies have cardiac abnormalities, such as impaired diastolic function, enhanced responsiveness to sympathetic stimulation and increased susceptibility to in vitro ischemia/reperfusion injury.  While this phenotype is often cited in the literature as being a precursor to disease, no study has directly tested whether offspring are more susceptible to cardiovascular risk factors, such as hypertension.  Establishing these relationships are important, because understanding comorbidities will help to predict, prevent and treat instances of heart disease.  Therefore, the first objective of this project is to test the hypothesis that adult offspring from hypoxic pregnancies are more susceptible to developing heart failure induced by chronic hypertension.  To address this hypothesis, we will study the effects of prenatal hypoxia on the hearts of adult rats chronically exposed to hypertensive stimuli.  In vivo heart function will be measured with echocardiography, and in vitro structure and cellular function will be investigated with histology and fluorescent microscopy, respectively.    Importantly, the study will investigate outcomes in both males and females, which addresses the urgent need for more gender-balanced cardiovascular research to improve cardiac health in women.       

How do postnatal diet and fetal hypoxia interact?

EC coupling

In addition to studying cardiac susceptibility to disease, the project also seeks to define the mechanistic basis for cardiac dysfunction in offspring from hypoxic pregnancies.  The Galli lab is currently investigating the hypothesis that prenatal hypoxia programmes maladaptive cardiomyocyte calcium handling which leads to the development of cardiac dysfunction.  Several lines of evidence suggest prenatal hypoxia alters the structure and function of the sarcoplasmic reticulum, an intracellular store of calcium that’s essential for excitation-contraction coupling.  Therefore, the second main aim of this project is to study the sex-dependent effects of prenatal hypoxia on aspects of sarcoplasmic reticulum physiology, including effects on ultrastructure, protein expression, calcium handling and regulation (particularly by adrenergic stimulation).  Within the timeframe of the project, we will identify the cellular pathways which programme cardiac dysfunction and increase the likelihood of developing heart disease.  Our broader aim is to use this information in the future to create novel therapeutic treatments for patients with heart disease.

Relevant Papers

Galli GLJ, Lock MC, Smith KLM, Giussani DA, Crossley DA 2nd. Effects of Developmental Hypoxia on the Vertebrate Cardiovascular System. Physiology (Bethesda). 2023 Mar 1;38(2):0. doi: 10.1152/physiol.00022.2022. Epub 2022 Nov 1. PMID: 36317939.

Walton SL, Singh RR, Tan T, Paravicini TM, Moritz KM. Late gestational hypoxia and a postnatal high salt diet programs endothelial dysfunction and arterial stiffness in adult mouse offspring. J Physiol. 2016 Mar 1;594(5):1451-63. doi: 10.1113/JP271067. Epub 2015 Oct 12. PMID: 26456386; PMCID: PMC4771779.

bottom of page