Maternal iron deficiency identifies critical windows for growth and cardiovascular development in the rat...

Imbalances in nutrition during pregnancy can lead to long-, as well as short-term consequences, a phenomenon known as fetal programming. However, there is little information about when the fetus is most sensitive to its environment during gestation. We hypothesize that different fetal systems are most vulnerable to nutritional stress during periods of maximal growth and differentiation. We used iron (Fe) deficiency, which causes hypertension in the offspring, to test this hypothesis. We examined development between embryonic day (E) 10.5 and 12.5, when cardiovascular development is maximal, using whole embryo culture. Female rats were fed Fe-deficient or control diet for 4 wk before mating and up to E10.5. The embryos were cultured for 48 h in 95% rat serum collected from males fed either a control or Fe-deficient diet. Growth was impaired and heart size increased in embryos taken from Fe-deficient mothers and cultured in deficient serum compared with control embryos cultured in control serum. To test whether restoring normal Fe levels could reverse these effects, we cultured embryos from control and deficient dams in either control or deficient medium. The yolk sac circulation of embryos from dams fed either diet cultured in deficient medium was less developed, with a thinner and less branched network than that in all embryos cultured in control serum. The heart was enlarged in embryos of deficient dams cultured in deficient serum compared with the heart size of those cultured in control serum. Culturing embryos in control serum reversed these changes. We conclude, therefore, that this period of cardiovascular organogenesis is one of the sensitive windows during which optimal Fe status is critical for normal development.