Maternal iron deficiency identifies critical windows for growth and cardiovascular development in the rat postimplantation embryo
Maternal iron deficiency identifies critical windows for growth and cardiovascular development in the rat postimplantation embryo
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DOI：
10.1093/jn/136.5.1171
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发表时间：
2006-05-01
影响因子：
4.2
通讯作者：
McArdle, HJ
中科院分区：
文献类型：
--
作者：
Andersen, HS;Gambling, L;McArdle, HJ
怀孕期间营养失衡可能会导致长期和短期后果，这种现象被称为胎儿编程。然而，关于胎儿在妊娠期间何时对其环境最敏感的信息很少。我们假设不同的胎儿系统在最大生长和分化期间最容易受到营养应激的影响。我们利用铁 (Fe) 缺乏（会导致后代出现高血压）来检验这一假设。我们使用全胚胎培养物检查了胚胎 (E) 10.5 至 12.5 天之间的发育，此时心血管发育最大。雌性大鼠在交配前 4 周喂食缺铁或对照饮食，直至 E10.5。将胚胎在从喂食对照或缺铁饮食的雄性大鼠收集的 95% 大鼠血清中培养 48 小时。与在对照血清中培养的对照胚胎相比，取自缺铁母亲并在缺铁血清中培养的胚胎生长受到损害，心脏尺寸增大。为了测试恢复正常的铁水平是否可以逆转这些影响，我们在对照或缺陷培养基中培养了对照和缺陷母鼠的胚胎。与在对照血清中培养的所有胚胎相比，在缺乏培养基中培养的两种饮食喂养的母鼠的胚胎的卵黄囊循环发育较差，具有更薄且分支更少的网络。与在对照血清中培养的胚胎相比，在缺陷血清中培养的缺陷母鼠的胚胎的心脏增大。在对照血清中培养胚胎逆转了这些变化。因此，我们得出结论，心血管器官发生的这一时期是敏感窗口之一，在此期间最佳的铁状态对于正常发育至关重要。
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.