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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\u2010replete or iron\u2010deficient pregnancy, we utilized mouse models expressing a range of ERFE levels: transgenic (TG) mice overexpressing ERFE, wild\u2010type (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\u2010deficient 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\u2010deficient conditions, maternal and embryo ERFE facilitate iron mobilization for embryonic erythropoiesis.<\/jats:p>","DOI":"10.1002\/ajh.26680","type":"journal-article","created":{"date-parts":[[2022,8,7]],"date-time":"2022-08-07T16:03:55Z","timestamp":1659888235000},"page":"1348-1358","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Erythroferrone contributes to iron mobilization for embryo erythropoiesis in iron\u2010deficient mouse pregnancies"],"prefix":"10.1002","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7397-0815","authenticated-orcid":false,"given":"Veena","family":"Sangkhae","sequence":"first","affiliation":[{"name":"Center for Iron Disorders, Department of Medicine, David Geffen School of Medicine University of California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vivian","family":"Yu","sequence":"additional","affiliation":[{"name":"Center for Iron Disorders, Department of Medicine, David Geffen School of Medicine University of California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Coffey","sequence":"additional","affiliation":[{"name":"Center for Iron Disorders, Department of Medicine, David Geffen School of Medicine University of California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly O.","family":"O'Brien","sequence":"additional","affiliation":[{"name":"Division of Nutritional Sciences Cornell University  Ithaca New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2830-5469","authenticated-orcid":false,"given":"Tomas","family":"Ganz","sequence":"additional","affiliation":[{"name":"Center for Iron Disorders, Department of Medicine, David Geffen School of Medicine University of California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3477-2397","authenticated-orcid":false,"given":"Elizabeta","family":"Nemeth","sequence":"additional","affiliation":[{"name":"Center for Iron Disorders, Department of Medicine, David Geffen School of Medicine University of California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,8,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a011866"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.117.155812"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/15648265030244S206"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/130.2.443S"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2005.02.015"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1753-4887.2011.00432.x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0029665113003637"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-05-786590"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1104742"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-03-0672"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020005745"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2996"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3945\/an.116.013961"},{"issue":"2","key":"e_1_2_10_15_1","first-page":"e35","article-title":"Erythroferrone: an erythroid regulator of Hepcidin and iron metabolism","volume":"2","author":"Coffey R","year":"2018","journal-title":"Hema"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.30247"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/nxab093"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/nxab156"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.17049"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021014054"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24333-z"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI127341"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/72.1.257S"},{"issue":"5","key":"e_1_2_10_24_1","first-page":"569","article-title":"Mutations in TMPRSS6 cause iron\u2010refractory iron deficiency anemia (IRIDA)","volume":"40","author":"Finberg 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