Introduction: Iron deficiency (ID) is the most common nutritional disorder in the world, and pregnant women are the most vulnerable group. ID during pregnancy can alter developmental trajectories and predispose offspring to cardiovascular diseases. Recently, we found evidence of cardiac dysfunction, increased mitochondrial content, and impaired mitochondrial respiration in the hearts of neonatal ID rats. Given that the perinatal heart is highly metabolically active and undergoing rapid changes, we hypothesized that perinatal ID would stimulate mitochondrial biogenesis and disrupt cardiomyocyte maturation postnatally.
Methods: Female Sprague Dawley rats were fed either an iron-restricted or an iron-replete diet before and during pregnancy. On postnatal days (PD)1, 14, and 28, ventricles were collected from male and female pups. Protein levels of mitochondrial biogenesis effectors (PGC-1α, AMPK : pAMPK ratio, Sirt1, Sirt3) and markers of cardiomyocyte maturation (α-MHC : β-MHC ratio) and damage (cTnI/T) were assessed by Western Blot. All data were analyzed by 2-way ANOVA.
Results: Male and female ID pups had reduced hemoglobin at PD1 and 14 (P<0.0001, both) but recovered by PD28. ID pups were also growth restricted at all time points (P<0.001, both) and had increased relative heart weights at PD1 and PD14. PGC-1α levels increased with age in both sexes (P=0.004, both) but there was no overall effect of perinatal ID. cTnT levels were decreased in ID pups of both sexes at PD28 (P=0.02), but not at other time points. No differences in cTnI were observed. The α-MHC : β-MHC ratio was decreased in female ID pups (P=0.007 overall), but not in males.
Conclusion: Our preliminary results indicate no upregulation of PGC-1α due to ID. Neonatal ID hearts show signs of increased cardiomyocyte damage and impaired maturation. Results for the remaining markers will provide insights into the mechanisms by which perinatal ID affects cardiac development and long-term cardiovascular health.