Holody 2019 MiP2019

From Bioblast
Claudia Holody
Sex-specific changes in neonatal cardiac mitochondrial function in response to perinatal iron deficiency.

Link: MiP2019

Holody CD, Woodman AG, Carpenter R, Bourque SL, Lemieux H (2019)

Event: MiP2019


Pregnant women are at a particularly high risk for developing iron deficiency (ID) and subsequent anemia due to blood volume expansion and increased demands from the fetal-placental unit [1]. Perinatal ID causes cardiovascular adaptations in the offspring, including cardiac enlargement [2]. This is likely a mechanism to increase cardiac output and maximize oxygen and nutrient delivery to tissues, but in turn increases the heart’s own energy requirements. Because the heart quickly becomes mitochondria-dependant after birth [3] and because iron is essential for oxidative energy production [4], we hypothesized that perinatal ID would alter cardiac mitochondrial function through the neonatal period.

Female rats were fed either an iron-restricted or an iron-replete diet before and during pregnancy. At birth, all dams were fed standard rat chow. Hearts from male and female offspring were collected at postnatal days (PD) 1, 14, and 28. Electron transport system and fatty acid Ξ²-oxidation capacities were assessed in permeabilized cardiac fibres using high-resolution respirometry. Mitochondrial content was measured by citrate synthase activity assay. Cytosolic superoxide anion levels were assessed using dihydroethidium stain visualized by fluorescence microscopy.

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 control pups (P<0.05). Heart weight relative to body weight was larger in ID pups at all ages (P<0.001). Mitochondrial content and respiratory capacity (O2 flux per fiber mass) increased with age. ID caused an overall increase in mitochondrial content in both sexes (P=0.03 for males; P=0.05 for females) at all timepoints. 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), and the succinate-pathway (electron flow through complex II; P=0.02) were reduced in ID male pups only, while complex IV was not affected. These results suggest a defect in complex III in ID males. ID did not change cardiac cytosolic superoxide levels in either sex.

Male, but not female, neonatal hearts adapt to perinatal ID by producing more mitochondria to compensate for reduced efficiency. Interestingly, this functional change is not accompanied by changes in cytosolic superoxide levels.

β€’ Bioblast editor: Plangger M, Tindle-Solomon L β€’ O2k-Network Lab: CA Edmonton Lemieux H

Labels: MiParea: Respiration, Comparative MiP;environmental MiP, Gender, Developmental biology 

Organism: Rat  Tissue;cell: Heart  Preparation: Permeabilized tissue 

Pathway: N, S, NS  HRR: Oxygraph-2k 


Holody CD(1,6), Woodman AG(2,6), Carpenter R(5), Bourque SL(1,2,3,6), Lemieux H(4,5,6)
  1. Depts of Pediatrics
  2. Pharmacology
  3. Anesthesiology & Pain Medicine
  4. Medicine
  5. Faculty Saint-Jean
  6. Women and Children’s Health Research Institute (WCHRI); Univ of Alberta, Edmonton, Canada. – [email protected]


  1. Breymann C (2015) Iron deficiency anemia in pregnancy. Semin Hematol 52:339-47.
  2. Woodman AG, Care AS, Mansour Y, Cherak, SJ, Panahi S, Gragasin FS, Bourque SL (2017) Modest and severe maternal iron deficiency in pregnancy are associated with fetal anaemia and organ-specific hypoxia in rats. Sci Rep 7:46573.
  3. Lopaschuk GD & Jaswal JS (2010) Energy metabolic phenotype of the cardiomyocyte during development, differentiation, and postnatal maturation. Journal of Cardiovascular Pharmacology 56:130-40.
  4. Rines AK & Hossein A (2013) Transition metals and mitochondrial metabolism in the heart. J Mol Cell Cardiol 55:50-57.
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