Role of Iron Metabolism-Related Genes in Prenatal Development: Insights from Mouse Transgenic Models

Abstract

Iron is an essential nutrient during all stages of mammalian development. Studies carried out over the last 20 years have provided important insights into cellular and systemic iron metabolism in adult organisms and led to the deciphering of many molecular details of its regulation. However, our knowledge of iron handling in prenatal development has remained remarkably under-appreciated, even though it is critical for the health of both the embryo/fetus and its mother, and has a far-reaching impact in postnatal life. Prenatal development requires a continuous, albeit quantitatively matched with the stage of development, supply of iron to support rapid cell division during embryogenesis in order to meet iron needs for erythropoiesis and to build up hepatic iron stores, (which are the major source of this microelement for the neonate). Here, we provide a concise overview of current knowledge of the role of iron metabolism-related genes in the maintenance of iron homeostasis in pre- and post-implantation development based on studies on transgenic (mainly knock-out) mouse models. Most studies on mice with globally deleted genes do not conclude whether underlying in utero iron disorders or lethality is due to defective placental iron transport or iron misregulation in the embryo/fetus proper (or due to both). Therefore, there is a need of animal models with tissue specific targeted deletion of genes to advance the understanding of prenatal iron metabolism.

Regulation of iron metabolism in HEC‐1A endometrium cells by macrophage‐derived factors and fractalkine

“…Iron transport is mediated by the endometrium towards the embryo by specific iron transporters, heme transporters, or extracellular vesicles (Hooda et al, 2014; Nakamura et al, 2020; Pandur et al, 2021). Therefore, iron deficiency in the mother has a deteriorating impact on fetal development causing growth retardation, and abnormal brain maturation (Abu‐Ouf & Jan, 2015; Chavarro et al, 2006; Georgieff, 2020; Kopeć et al, 2021).…”

“…Iron metabolism of the mother, including the endometrium, is crucial in fertility (Cerami, 2017; Sangkhae et al, 2020). Iron deficiency can decrease the chance of fertilization (Chavarro et al, 2006; Kopeć et al, 2021). Moreover, iron availability acts as a regulatory factor of endometrial receptivity as well as embryo implantation.…”

The Effects of Vitamins and Micronutrients on Helicobacter pylori Pathogenicity, Survival, and Eradication: A Crosstalk between Micronutrients and Immune System

“…The regulation of iron concentration relies on hepcidin, ferroportin, and hypoxia-inducible factor-2 (HIF2). HIF2 regulates the production of proteins involved in iron absorption, while hepcidin, a liver-derived hormone, blocks ferroportin to inhibit iron absorption, storage, and recycling in duodenal enterocytes, hepatocytes, and reticuloendothelial macrophages, respectively [ 225 ]. In addition to general iron hemostasis, nutritional immunity as a dynamic mechanism allows the host to respond to pathogenic attacks and prevents bacterial growth by restricting bacterial access and intracellular availability to iron [ 226 ].…”

Fractalkine Improves the Expression of Endometrium Receptivity-Related Genes and Proteins at Desferrioxamine-Induced Iron Deficiency in HEC-1A Cells

“…Thus, the maternal iron status is fundamental [7][8][9]. Iron deficiency affects cell division and pattern formation, as well as the development and maturation of the central nervous system, since iron is crucial in myelin sheath formation around the neuronal axons [9][10][11][12]. Maternal iron disorders increase retardation of embryonic development and/or lethality due to faulty iron transport through the placenta [12,13].…”