Introduction: Early life iron deficiency (ID) can alter developmental trajectories and cause long-term cardiovascular dysfunction in offspring. The heart becomes energetically dependent on mitochondria soon after birth and therefore disturbances in energy metabolism could impact cardiac development. Since iron is a component of the electron transport system (ETS), we hypothesized that perinatal ID would alter neonatal cardiac mitochondrial function.
Methods: Female rats were fed either an iron-restricted or control diet before and during pregnancy and offspring hearts were studied. ETS and fatty acid β-oxidation (FAO) capacities were assessed using high-resolution respirometry. Mitochondrial content was measured by citrate synthase activity assay. Cytosolic superoxide was quantified using dihydroethidium stain visualized by fluorescence microscopy. The effects of iron restriction and postnatal day (PD) were analyzed using a mixed-effects model.
Results: Hemoglobin levels were reduced in ID pups at PD1 (P<0.001) and PD14 (P=0.008 for males; P=0.02 for females) but were no longer different at PD28 (P=0.85 for males; P=0.58 for females). Body weights of ID pups were reduced at all ages compared to controls (P<0.001). Heart weight relative to body weight was larger in ID pups at all ages (P<0.001). ID caused an overall increase in cardiac mitochondrial content in both sexes (P=0.03 for males; P=0.05 for females). When normalized for mitochondrial content, mitochondrial respiration through the NADH-pathway (electron flow through complex I; P=0.03), the NS-pathway (electron flow through complexes I and II; P=0.06), the succinate-pathway (electron flow through complex II; P=0.02), and the FAO-pathway (P=0.01) was reduced in ID males only, while complex IV was not affected in either sex. ID did not change cytosolic superoxide levels in either sex (P>0.05).
Conclusion: The neonatal heart adapts to ID by increasing mitochondrial content, however, only ID male hearts showed reduced mitochondrial efficiency. The results suggest a defect in complex III in ID males.
Andrew Woodman– MD-PhD Candidate, University of Alberta
Rowan Carpenter– Undegraduate Student, University of Alberta
Hélène Lemieux– Associate Professor, University of Alberta, Faculty Saint-Jean
Stephane Bourque– Assistant Professor, University of Alberta