Molecular Nutrition

Effects of Heme Iron on Reproductive Performance and Iron-Regulated Gene Expressions in Tissues of Pregnant Mice

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  • Key Laboratory of Animal Nutrition and Feed Science of Yunnan Province, College of Animal Science and Technology, Yunnan Agricultural University, Kunming 650021, China

Received date: 2016-12-01

  Online published: 2017-06-07

Abstract

This study was conducted to compare the effects of heme iron (Fe) and ferrous sulfate (FeSO4) on reproductive performance, the Fe content in pregnant mice tissues and fetal mice, and the expressions of Fe-regulated genes[hepcidin, ferroportin (Fpn), feline leukemia virus subgroup C receptor (Flvcr), heme carrier protein (HCP), transferrin receptor 1 (Tfr1), transferrin receptor 2 (Tfr2) and divalent metal transporter 1 (DMT1)] in tissues of pregnant mice. Eighty Kunming female mice with similar body condition at 2 months of age were selected and randomly divided into 8 groups with 10 mice per group. The groups were control group, Fe deficiency group, heme Fe (15, 60 and 90 mg/kg) groups and FeSO4 (75, 300 and 450 mg/kg) groups. Since pregnant, control group was fed normal diet (a basal diet supplemented with 400 mg/kg FeSO4); the other groups were fed the basal diet, and were injected 40 mg/kg deferoxamine to induce Fe deficiency model at 10 to 13 d of pregnant; heme Fe and FeSO4 were supplemented in heme Fe groups and FeSO4 groups from 14 d of pregnant, while none of them was supplemented in Fe deficiency group. The experiment was carried out at 1 to 20 d of pregnant. The results showed as follows:1) the weight of fetal mice in 60 mg/kg group was significantly higher than that in control group and Fe deficiency group (P<0.01). 2) Blood hemoglobin (HGB) content, red blood cell (RBC) and hematocrit (HCT) in 60 mg/kg heme Fe group and 450 mg/kg FeSO4 group were significantly higher than those in Fe deficiency group (P<0.01). 3) The Fe content in the fetal mice in 60 mg/kg heme Fe group was significantly higher than that in control group and FeSO4 groups (P<0.01); the Fe content in liver, spleen and placenta was the highest in450 mg/kg FeSO4 group. 4) The expression of hepcidin in liver of pregnant mice was higher in 90 mg/kg heme Fe group and 450 mg/kg FeSO4 group, which was significantly higher than that in Fe deficiency group and control group (P<0.01); the expressions of Fpn and Tfr2 in liver in 15 mg/kg heme Fe group were higher, which were significantly higher than those in Fe deficiency group and control group (P<0.01); the expressions of Tfr1 and Flvcr in liver in 60 mg/kg heme Fe group were higher, which were significantly higher than those in Fe deficiency group and control group (P<0.01); the expression of Tfr1 in liver in 75 mg/kg FeSO4 group was higher, which was significantly higher than that in Fe deficiency group and control group (P<0.01). 5) Fpn, HCP, DMT1 and Flvcr expressions in duodenum of pregnant mice in Fe deficiency group were significantly higher than those in control group (P<0.01). 6) Placenta Fpn, HCP, DMT1, Flvcr and Tfr1 expressions were significantly higher than those in control group (P<0.01); the expression of hepcidin in placenta in 90 mg/kg heme Fe and 450 mg/kg FeSO4 was higher, which was significantly higher than that in Fe deficiency group and control group (P<0.01). 7) The Fe content of fetal mice was the highest when heme Fe was 61.00 mg/kg or FeSO4 was 336.11 mg/kg; the Fe content in liver of pregnant mice was the highest when heme Fe was 93.49 mg/kg. In conclusion, the supplementation of heme Fe and FeSO4 at proper levels can increase the weight of fetal mice, regulate the expressions of Fe-regulating genes in target tissues of pregnant mice, and increase the body Fe content of pregnancy mice and 20 d fetal mice; HCP and Flvcr play critical roles in the intestinal absorption or placental transport of heme Fe, while intestinal absorption and placental transport of FeSO4 mainly rely on DMT1 and Tfr2.

Cite this article

LI Meiquan, ZHANG Chunyong, JI Qiaoqing, CHEN Kelin, GUO Rongfu . Effects of Heme Iron on Reproductive Performance and Iron-Regulated Gene Expressions in Tissues of Pregnant Mice[J]. Chinese Journal of Animal Nutrition, 2017 , 29(6) : 1996 -2009 . DOI: 10.3969/j.issn.1006-267x.2017.06.021

References

[1] 白松涛.妊娠期缺铁性贫血治疗方法的系统性评价[D].硕士学位论文.遵义:遵义医学院,2012.

[2] 赵惠君.儿童缺铁和缺铁性贫血的防治[J].实用儿科临床杂志,2012,27(3):163-165.

[3] CAO C,O'BRIEN K O.Pregnancy and iron homeostasis:an update[J].Nutrition Reviews,2012,71(1):35-51.

[4] FURUYAMA K,KANEKO K,VARGAS V P D.Heme as a magnificent molecule with multiple missions:heme determines its own fate and governs cellular homeostasis[J].The Tohoku Journal of Experimental Medicine,2007,213(1):1-16.  

[5] GANZ T.Systemic iron homeostasis[J].Physiological Reviews,2013,93(4):1721-1741.  

[6] FINBERG K E.Regulation of systemic iron homeostasis[J].Current Opinion in Hematology,2013,20(3):208-214.  

[7] SINGH B,ARORA S,AGRAWAL P,et al.Hepcidin:a novel peptide hormone regulating iron metabolism[J].Clinica Chimica Acta,2011,412(11/12):823-830.

[8] PFAFFL M W.A new mathematical model for relative quantification in real-time RT-PCR[J].Nucleic Acids Research,2001,29(9):e45.

[9] 解超,王宝维,葛文华,等.鹅血红素对患缺铁性贫血症幼龄大鼠生长发育、铁代谢和器官组织元素分布的影响[J].动物营养学报,2015,27(2):408-417.

[10] 游开绍,吴斌,赵子庆,等.氯高铁血红素与富马酸亚铁治疗小儿缺铁性贫血的疗效比较[J].中国新药与临床杂志,1995,14(4):211-213.

[11] 钟才云,马凤楼,蔡凤鸣,等.血红素铁治疗女大学生缺铁性贫血的研究[J].中国校医,1995,9(3):167-169.

[12] DE CARLI E,LOBO A R,SALES C H,et al.Short-term dietary magnesium restriction lowers spleen iron concentrations in growing rats fed a high-fat diet[J].LWT:Food Science and Technology,2014,59(2):1298-1303.  

[13] PIGEON C,ILYIN G,COURSELAUD B,et al.A new mouse liver-specific gene,encoding a protein homologous to human antimicrobial peptide hepcidin,is overexpressed during iron overload[J].Journal of Biological Chemistry,2001,276(11):7811-7819.  

[14] BOLONDI G,GARUTI C,CORRADINI E,et al.Altered hepatic BMP signaling pathway in human HFE hemochromatosis[J].Blood Cells,Molecules,and Diseases,2010,45(4):308-312.  

[15] DONOVAN A,BROWNLIE A,ZHOU Y,et al.Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter[J].Nature,2000,403(6771):776-781.  

[16] BOUMAIZA M,JAOUEN M,DESCHEMIN J C,et al.Expression and purification of a new recombinant camel hepcidin able to promote the degradation of the iron exporter ferroportin1[J].Protein Expression and Purification,2015,115:11-18

[17] VINCHI F,INGOGLIA G,CHIABRANDO D,et al.Heme exporter FLVCR1a regulates heme synthesis and degradation and controls activity of cytochromes P450[J].Gastroenterology,2014,146(5):1325-1338.  

[18] WYLLIE J C,KAUFMAN N.An electron microscopic study of heme uptake by rat duodenum[J].Laboratory Investigation,1982,47(5):471-476.

[19] MORENO-CARRALERO M I,MUÑOZ-MUÑOZ J A,CUADRADO-GRANDE N,et al.A novel mutation in the SLC40A1 gene associated with reduced iron export in vitro[J].American Journal of Hematology,2014,89(7):689-694.  

[20] SHAYEGHI M,LATUNDE-DADA G O,OAKHILL J S,et al.Identification of an intestinal heme transporter[J].Cell,2005,122(5):789-801.  

[21] LEONG W I,BOWLUS C L,TALLKVIST J,et al.DMT1 and FPN1 expression during infancy:developmental regulation of iron absorption[J].American Journal of Physiology:Gastrointestinal and Liver Physiology,2003,285(6):G1153-G1161.

[22] GARCIA-VALDES L,CAMPOY C,HAYES H,et al.The impact of maternal obesity on iron status,placental transferrin receptor expression and hepcidin expression in human pregnancy[J].International Journal of Obesity,2015,39(4):571-578.  

[23] BASTIN J,DRAKESMITH H,REES M,et al.Localisation of proteins of iron metabolism in the human placenta and liver[J].British Journal of Haematology,2006,134(5):532-543.  

[24] 李四保,刘玉峰,王玉梅,等.血清铁调素及胎盘膜铁转运蛋白1在母婴铁转运中的作用[J].中华血液学杂志,2015,36(4):307-311.

[25] BYON J C H,CHEN J,DOTY R T,et al.FLVCR is necessary for erythroid maturation,may contribute to platelet maturation,but is dispensable for normal hematopoietic stem cell function[J].Blood,2013,122(16):2903-2910.  
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