Molecular Nutrition Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia.
Iron Metabolism Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia.
Int J Mol Sci. 2023 Sep 21;24(18):14379. doi: 10.3390/ijms241814379.
In order to supply adequate iron during pregnancy, the levels of the iron regulatory hormone hepcidin in the maternal circulation are suppressed, thereby increasing dietary iron absorption and storage iron release. Whether this decrease in maternal hepcidin is caused by changes in factors known to regulate hepcidin expression, or by other unidentified pregnancy factors, is not known. To investigate this, we examined iron parameters during pregnancy in mice. We observed that hepatic iron stores and transferrin saturation, both established regulators of hepcidin production, were decreased in mid and late pregnancy in normal and iron loaded dams, indicating an increase in iron utilization. This can be explained by a significant increase in maternal erythropoiesis, a known suppressor of hepcidin production, by mid-pregnancy, as indicated by an elevation in circulating erythropoietin and an increase in spleen size and splenic iron uptake. Iron utilization increased further in late pregnancy due to elevated fetal iron demand. By increasing maternal iron levels in late gestation, we were able to stimulate the expression of the gene encoding hepcidin, suggesting that the iron status of the mother is the predominant factor influencing hepcidin levels during pregnancy. Our data indicate that pregnancy-induced hepcidin suppression likely occurs because of reductions in maternal iron reserves due to increased iron requirements, which predominantly reflect stimulated erythropoiesis in mid-gestation and increased fetal iron requirements in late gestation, and that there is no need to invoke other factors, including novel pregnancy factor(s), to explain these changes.
为了在妊娠期间提供足够的铁，母体循环中的铁调节激素铁调素水平受到抑制，从而增加膳食铁吸收和储存铁释放。母体铁调素的这种减少是由已知调节铁调素表达的因素变化引起的，还是由其他未识别的妊娠因素引起的，目前尚不清楚。为了研究这一点，我们在小鼠中检查了妊娠期间的铁参数。我们观察到，在正常和铁负荷的母体中，肝脏铁储存和转铁蛋白饱和度均为铁调素产生的既定调节剂，在妊娠中期和晚期均降低，表明铁利用增加。这可以通过母体红细胞生成的显著增加来解释，红细胞生成是铁调素产生的已知抑制剂，这表明循环促红细胞生成素升高和脾脏增大以及脾脏铁摄取增加。由于胎儿对铁的需求增加，妊娠晚期铁的利用进一步增加。通过在妊娠晚期增加母体铁水平，我们能够刺激编码铁调素的基因的表达，这表明母体的铁状态是影响妊娠期间铁调素水平的主要因素。我们的数据表明，妊娠诱导的铁调素抑制可能是由于母体铁储备减少所致，这主要反映了妊娠中期红细胞生成增加和妊娠晚期胎儿铁需求增加，并且不需要援引其他因素，包括新的妊娠因素，来解释这些变化。
