Erythroferrone contributes to iron mobilization for embryo erythropoiesis in iron‐deficient mouse pregnancies. Issue 10 (16th August 2022)

• Record Type: Journal Article
• Authors: Sangkhae, Veena; Yu, Vivian; Coffey, Richard; O'Brien, Kimberly O.; Ganz, Tomas; Nemeth, Elizabeta
• Is Part Of: American journal of hematology. Volume 97:Issue 10(2022)
• Page Start: 1348
• Page End: 1358
• Publication Date: 2022-08-16
• Subjects: Hematology -- Periodicals; 616.15
• DOI: 10.1002/ajh.26680
• Languages: English
• ISSNs: 0361-8609

Abstract

Abstract: Erythroferrone (ERFE) is an erythroblast‐secreted regulator of iron metabolism. The production of ERFE increases during stress erythropoiesis, leading to decreased hepcidin expression and mobilization of iron. Pregnancy requires a substantial increase in iron availability to sustain maternal erythropoietic expansion and fetal development and is commonly affected by iron deficiency. To define the role of ERFE during iron‐replete or iron‐deficient pregnancy, we utilized mouse models expressing a range of ERFE levels: transgenic (TG) mice overexpressing ERFE, wild‐type (WT), and ERFE knockout (KO) mice. We altered maternal iron status using diets with low or standard iron content and performed the analysis at E18.5. Iron deficiency increased maternal ERFE in WT pregnancy. Comparing different maternal genotypes, ERFE TG dams had lower hepcidin relative to their liver iron load but similar hematological parameters to WT dams on either diet. In ERFE KO dams, most hematologic and iron parameters were comparable to WT, but mean corpuscular volume (MCV) was decreased under both iron conditions. Similar to dams, TG embryos had lower hepcidin on both diets, but their hematologic parameters did not differ from those of WT embryos. ERFE KO embryos had lower MCV than WT embryos on both diets. The effect was exacerbated under iron‐deficient conditions where ERFE KO embryos had higher hepcidin, lower Hb and Hct, and lower brain iron concentration compared to WT embryos, indicative of iron restriction. Thus, under iron‐deficient conditions, maternal and embryo ERFE facilitate iron mobilization for embryonic erythropoiesis. Abstract : Iron is necessary for a healthy pregnancy. We studied the role of the iron‐regulatory hormone erythroferrone (ERFE) in pregnancy by comparing outcomes in mice with varying levels of ERFE. When dams were iron‐deficient, embryo ERFE ensured embryo hepcidin was suppressed to facilitate iron delivery to the brain and for the production of red blood cells to carry oxygen to tissues.