The Long-Term Cardiovascular and Behavioural Consequences of Maternal Iron Restriction During Gestation in Rat Offspring
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Maternal and fetal stressors during development can permanently alter various physiological functions and impact long-term health. These alterations are said to be programmed because they persist long after the original insult. Current evidence indicates that iron deficiency (ID) during pregnancy can induce a host of long-term programming effects, including cardiovascular complications and behavioural deficits. Despite the relevance of ID as a model of developmental programming, these effects have not been extensively studied. The purpose of the present series of experiments was to develop a model of maternal ID throughout pregnancy to study its long-term cardiovascular and behavioural consequences in neonatal and adult offspring. Female rats were fed either a low iron diet (3 mg/kg or 10 mg/kg Fe) or a control diet (> 225 mg/kg Fe) prior to and throughout gestation. At birth, all dams were fed a control diet (270 mg/kg Fe). This treatment caused altered growth trajectories which persisted in adulthood. Adult perinatal ID (PID) offspring, despite showing no signs of anemia at that time, had persistent elevations in arterial pressure (AP), as well as enhanced responsiveness of AP to high and low sodium intake. These animals also had altered responsiveness of renal medullary blood flow to changes in AP. PID offspring also had altered function of intrarenal and vascular nitric oxide signaling. Similar studies performed in acute ID animals revealed opposite trends in intrarenal and vascular NOS function, as well as in effects on the cardiovascular system. In addition to the cardiovascular effects, adult PID male offspring exhibited a number of behavioural changes, as assessed by monitoring locomotor activity in their home cages (by radiotelemetry) as well as in a novel environment. PID male offspring also performed poorly in a Morris water maze compared to controls. These differences were not observed in female PID animals. In summary, these studies provide evidence that ID during gestation has deleterious effects on various aspects of the offspring’s physiology. Given the global incidence of ID, as well as its propensity to afflict pregnant women, developmental programming from this condition could have profound implications on global health.