Preterm Piglets Born by Cesarean Section as a Suitable Animal Model for the Study of Iron Metabolism in Premature Infants.

Preterm infants are most at risk of iron deficiency. However, our knowledge of the regulation of iron homeostasis in preterm infants is poor. The main goal of our research was to develop and validate an animal model of human prematurity to assess iron status in preterm infants. We performed a cesarean section on sows on the 109th day of pregnancy, which corresponds to the last trimester of human pregnancy. Preterm piglets showed decreased body weight, red blood cell indices, plasma iron level and transferrin saturation. Interestingly, higher hepatic and splenic non-heme iron content and plasma and hepatic ferritin levels were found in premature piglets compared with term ones. In addition, premature piglets showed higher mRNA levels of iron-regulatory hormone hepcidin in the liver than term animals, which have not been reflected in higher plasma hepcidin-25 levels. We also showed changes in hepcidin regulators, including hepatic bone morphogenetic protein 6, plasma erythroferrone and growth differentiation factor 15 in preterm piglets. Consequently, no difference was observed in iron-exporter ferroportin levels in the spleen and liver. Overall, it seems that premature piglets show a pattern of iron metabolism characteristic of functional iron deficiency and iron accumulation in the tissue.早产婴儿是铁缺乏症的最高危人群。然而，目前学界对早产婴儿铁稳态（iron homeostasis）的调控机制认知仍较为匮乏。本研究的核心目标为构建并验证一款可用于评估早产婴儿铁营养状态的人类早产动物模型。本研究对妊娠第109天的母猪实施剖宫产术，该时间节点对应人类妊娠的最后三个月，即妊娠晚期。早产仔猪表现为体重降低、红细胞参数、血浆铁水平及转铁蛋白饱和度均出现下降。值得注意的是，与足月仔猪相比，早产仔猪的肝脏及脾脏非血红素铁含量、血浆与肝脏铁蛋白（ferritin）水平均更高。此外，早产仔猪肝脏内铁调节激素铁调素（hepcidin）的mRNA表达水平高于足月仔猪，但这一差异并未体现在血浆hepcidin-25水平的升高上。本研究还观察到早产仔猪体内铁调素调控因子的变化，包括肝脏骨形态发生蛋白6（bone morphogenetic protein 6）、血浆红细胞铁调素调节蛋白（erythroferrone）及生长分化因子15（growth differentiation factor 15）的水平发生改变。因此，脾脏与肝脏内铁输出蛋白铁转运蛋白（ferroportin）的表达水平未出现显著差异。综上，早产仔猪呈现出功能性铁缺乏伴组织铁蓄积的铁代谢特征模式。