Maternal iron homeostasis: effect on placental development and function

Abstract

Iron is an essential mineral that participates in oxygen transport, DNA synthesis and repair, and as a cofactor for various cellular processes. Iron deficiency is the most common nutritional deficiency worldwide. Due to blood volume expansion and demands from the fetal-placental unit, pregnant women are one of the populations most at risk of developing iron deficiency. Iron deficiency during pregnancy poses major health concerns for offspring, including intrauterine growth restriction and long-term health complications. Although the underlying mechanisms remain unclear, maternal iron deficiency may indirectly impair fetal growth through changes in the structure and function of the placenta. Since the placenta forms the interface between mother and baby, understanding how the placenta changes in iron deficiency may yield new diagnostic indices of fetal stress in affected pregnancies, thereby leading to earlier interventions and improved fetal outcomes. In this review, we compile current data on the changes in placental development and function that occur under conditions of maternal iron deficiency, and discuss challenges and perspectives on managing the high incidence of iron deficiency in pregnant women.

Disordered Maternal and Fetal Iron Metabolism Occurs in Preterm Births in Human

“…Likewise, the iron concentrations in the cord blood were much lower than that in full-term births, revealing remarkable iron deficiency in the developing fetuses prior to preterm births ( Figure 1(d) ), P < 0.001). Previous animal studies have portrayed the placenta as a selfish organ since the placenta stores an adequate amount of iron to ensure its functions in maternal iron deficiency [ 13 ]. However, a recent study conducted by Irwinda et al indicated that the placental iron stores in women with preterm births were much lower than that in women full-term births [ 28 ].…”

“…Greatly decreased placental iron stores were found in participants with preterm births relative to those with full-term births as evidenced by decreased placental tissue iron ( Figure 1(e) ), P < 0.05) and diminished mass of ferritin ( Figure 2(c) ), P < 0.05). Despite no direct experimental evidence, the maternal hepcidin is assumed to control the placental iron transport through syncytiotrophoblasts [ 13 , 36 , 37 ]. The mass of FPN in placentas was greatly elevated in the preterm group, compared to the full-term group ( Figure 2(c) ), P < 0.05) presumably attributable to the diminished maternal hepcidin levels ( Figure 2(b) ), P < 0.001), implying a direct regulation of maternal hepcidin on the FPN concentrations in syncytiotrophoblasts.…”

“…Meanwhile, the placenta is an important organ for iron storage and plays a crucial role in supplying iron to the fetus throughout pregnancy to support fetal growth and development. In maternal iron deficiency, the placenta would give the priority to maintain sufficient iron stores to support its functions and to deliver iron to the fetus despite the low iron levels in maternal blood [ 13 ]. However, in analogy to a recently reported study [ 28 ], the placental iron stores were apparently compromised under preterm condition ( Figure 1(e) ).…”

“…Iron is a necessary metal for nearly all species and is involved in a broad range of biological processes, including oxygen transport, electron transport, and DNA synthesis [ 13 , 14 ]. In pregnancies, iron transported through the placenta from the mother to the fetus is critical for embryonic development and fetal growth.…”

Iron deficiency, pregnancy, and neonatal development

“…Most animal models of diet‐induced ID have found that placental weight and diameter do not significantly differ between iron‐deficient animals or animals with an adequate iron intake 14,47 . However, one study of dietary‐iron‐restricted rats found that, although maternal iron restriction had no effect on placental weight at gestational day 13.5—the equivalent of a human second trimester—it did result in a 10% increase in placental weight at term and that this effect was mainly seen via an expansion in the junctional zone of the placenta 43 . We did not find convincing evidence of human studies supporting these results, with only a small cross‐sectional study of women delivering healthy term babies seeming to show a nonsignificant decrease in weight between placentas from women with low serum ferritin ( n = 26; mean ferritin 7.65 ± 1.28 μg/L; placental weight 0.59 ± 0.13 kg) versus those with normal serum ferritin ( n = 18; mean ferritin 34.2 ± 12.8 μg/L; placental weight 0.65 ± 0.21 kg) 48 …”