scholarly journals THE EFFECTS OF IRON DEFICIENCY ON THE HEPATOCYTE: A BIOCHEMICAL AND ULTRASTRUCTURAL STUDY

1971 ◽  
Vol 48 (1) ◽  
pp. 79-90 ◽  
Author(s):  
Peter R. Dallman ◽  
Joseph R. Goodman
Keyword(s):  
Iron Deficiency ◽  
Cytochrome B5 ◽  
Deficient Diet ◽  
Fourfold Increase ◽  
Iron Administration ◽  
Iron Deprivation ◽  
Complete Diet ◽  
Iron Deficient ◽  
Mitochondrial Number ◽  
Cytochrome P 450

Effects of iron deficiency on the hepatocyte were studied quantitatively in the rat by combining ultrastructural and biochemical techniques. After 3–8 wk of an iron-deficient diet, the percentage of cytoplasm occupied by mitochondria increased progressively compared with complete diet values. The increment resulted primarily from an enlargement of individual mitochondria rather than from an increased mitochondrial number. Many mitochondria were completely divided by a double membrane, often at a point of constriction. After 2 days of iron administration, mitochondria were of heterogeneous size, shape, and electron opacity. After 5 days, essentially all mitochondria had become normal in configuration. The rate of reversal of the morphological abnormality was more rapid than would be anticipated if it coincided with known rates of renewal of mitochondrial DNA or protein. The concentrations of mitochondrial cytochromes were more rapidly depressed as a result of iron deprivation than those of microsomal cytochromes. Cytochromes c and a were decreased after 3 and 8 wk of exposure to the deficient regimen. Cytochrome P 450 was not decreased after a 3 wk exposure to the deficient diet and responded normally to phenobarbital treatment with a fourfold increase in total hepatic content; its concentration was depressed only after 8 wk of exposure to the deficient diet. There was no reduction in cytochrome b5 concentration.

Developmental iron deficiency dysregulates TET activity and DNA hydroxymethylation in the rat hippocampus and cerebellum

2022 ◽  
Author(s):  
Amanda K. Barks ◽  
Montana M. Beeson ◽  
Timothy C. Hallstrom ◽  
Michael K. Georgieff ◽  
Phu V. Tran
Keyword(s):  
Iron Deficiency ◽  
Neural Circuit ◽  
Epigenetic Modification ◽  
Rat Hippocampus ◽  
Dietary Iron ◽  
Deficient Diet ◽  
Dna Hydroxymethylation ◽  
Iron Treatment ◽  
Iron Deficient ◽  
Increased Risk

Iron deficiency (ID) during neurodevelopment is associated with lasting cognitive and socioemotional deficits, and increased risk for neuropsychiatric disease throughout the lifespan. These neurophenotypical changes are underlain by gene dysregulation in the brain that outlasts the period of ID; however, the mechanisms by which ID establishes and maintains gene expression changes are incompletely understood. The epigenetic modification 5-hydroxymethylcytosine (5hmC), or DNA hydroxymethylation, is one candidate mechanism because of its dependence on iron-containing TET enzymes. The aim of the present study was to determine the effect of fetal-neonatal ID on regional brain TET activity, Tet expression, and 5hmC in the developing rat hippocampus and cerebellum, and to determine whether changes are reversible with dietary iron treatment. Timed pregnant Sprague-Dawley rats were fed iron deficient diet (ID; 4 mg/kg Fe) from gestational day (G)2 to generate iron deficient anemic (IDA) offspring. Control dams were fed iron sufficient diet (IS; 200 mg/kg Fe). At postnatal day (P)7, a subset of ID-fed litters was randomized to IS diet, generating treated IDA (TIDA) offspring. At P15, hippocampus and cerebellum were isolated for subsequent analysis. TET activity was quantified by ELISA from nuclear proteins. Expression of Tet1, Tet2, and Tet3 was quantified by qPCR from total RNA. Global %5hmC was quantified by ELISA from genomic DNA. ID increased DNA hydroxymethylation (p=0.0105), with a corresponding increase in TET activity (p<0.0001) and Tet3 expression (p<0.0001) in the P15 hippocampus. In contrast, ID reduced TET activity (p=0.0016) in the P15 cerebellum, with minimal effect on DNA hydroxymethylation. Neonatal dietary iron treatment resulted in partial normalization of these changes in both brain regions. These results demonstrate that the TET/DNA hydroxymethylation system is disrupted by developmental ID in a brain region-specific manner. Differential regional disruption of this epigenetic system may contribute to the lasting neural circuit dysfunction and neurobehavioral dysfunction associated with developmental ID.

scholarly journals The Treatment of Iron Deficiency Anemia

Blood ◽  
1955 ◽  
Vol 10 (6) ◽  
pp. 567-581 ◽  
Author(s):  
DANIEL H. COLEMAN ◽  
ALEXANDER R. STEVENS ◽  
CLEMENT A. FINCH
Keyword(s):  
Iron Deficiency ◽  
Gastrointestinal Symptoms ◽  
The Body ◽  
Deficiency Anemia ◽  
Deficient Diet ◽  
Significant Group ◽  
Body Iron ◽  
Iron Stores ◽  
Iron Deficient ◽  
Full Complement

Abstract In the normal individual the amount of iron absorbed and lost from the body each day is exceedingly small. There are certain periods during life when body iron requirements are increased; the most important of these is infancy. Here, existing iron stores are rapidly depleted, and a deficient diet can soon produce iron deficiency. Once a full complement of body iron has been accrued, the adult is independent of iron intake and becomes iron deficient only through blood loss. In the production of iron deficiency, iron stores are exhausted before anemia appears. If any question in diagnosis from usual laboratory tests exists, the direct. examination of marrow for hemosiderin will establish the diagnosis. It is of obvious importance to confirm the diagnosis by specific therapy and to determine the cause of the iron depletion. Response to oral iron is highly predictable and failure of response usually in dictates a mistaken diagnosis. In a small but significant group of patients, either unable to take iron because of gastrointestinal symptoms, unable to absorb iron, or in need of iron reserves, parenteral administration of iron has distinct advantages. The saccharated oxide of iron is an effective preparation for this purpose.

scholarly journals Bacterial Compound N,N-Dimethylhexadecylamine Modulates Expression of Iron Deficiency and Defense Response Genes in Medicago truncatula Independently of the Jasmonic Acid Pathway

Plants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 624 ◽  
Author(s):  
Vicente Montejano-Ramírez ◽  
Ernesto García-Pineda ◽  
Eduardo Valencia-Cantero
Keyword(s):  
Gene Expression ◽  
Salicylic Acid ◽  
Iron Deficiency ◽  
Jasmonic Acid ◽  
Pseudomonas Syringae ◽  
Medicago Truncatula ◽  
Abiotic Stresses ◽  
Biotic And Abiotic Stresses ◽  
Iron Deprivation ◽  
Iron Deficient

Plants face a variety of biotic and abiotic stresses including attack by microbial phytopathogens and nutrient deficiencies. Some bacterial volatile organic compounds (VOCs) activate defense and iron-deficiency responses in plants. To establish a relationship between defense and iron deficiency through VOCs, we identified key genes in the defense and iron-deprivation responses of the legume model Medicago truncatula and evaluated the effect of the rhizobacterial VOC N,N-dimethylhexadecylamine (DMHDA) on the gene expression in these pathways by RT-qPCR. DMHDA increased M. truncatula growth 1.5-fold under both iron-sufficient and iron-deficient conditions compared with untreated plants, whereas salicylic acid and jasmonic acid decreased growth. Iron-deficiency induced iron uptake and defense gene expression. Moreover, the effect was greater in combination with DMHDA. Salicylic acid, Pseudomonas syringae, jasmonic acid, and Botrytis cinerea had inhibitory effects on growth and iron response gene expression but activated defense genes. Taken together, our results showed that the VOC DMHDA activates defense and iron-deprivation pathways while inducing a growth promoting effect unlike conventional phytohormones, highlighting that DMHDA does not mimic jasmonic acid but induces an alternative pathway. This is a novel aspect in the complex interactions between biotic and abiotic stresses.

Identification of differentially expressed genes in response to dietary iron deprivation in rat duodenum

2005 ◽  
Vol 288 (5) ◽  
pp. G964-G971 ◽  
Author(s):  
James F. Collins ◽  
Christina A. Franck ◽  
Kris V. Kowdley ◽  
Fayez K. Ghishan
Keyword(s):  
Iron Deficiency ◽  
Real Time ◽  
Real Time Pcr ◽  
Iron Transport ◽  
Dietary Iron ◽  
Cancer Resistance ◽  
Novel Genes ◽  
Copper Absorption ◽  
Iron Deprivation ◽  
Iron Deficient

We sought to identify novel genes involved in intestinal iron absorption by inducing iron deficiency in rats during postnatal development from the suckling period through adulthood. We then performed comparative gene chip analyses (RAE230A and RAE230B chips; Affymetrix) with cRNA derived from duodenal mucosa. Real-time PCR was used to confirm changes in gene expression. Genes encoding the apical iron transport-related proteins [ divalent metal transporter 1 (DMT1) and duodenal cytochrome b] were strongly induced at all ages studied, whereas increases in mRNA encoding the basolateral proteins iron-regulated gene 1 and hephaestin were observed only by real-time PCR. In addition, transferrin receptor 1 and heme oxygenase 1 were induced. We also identified induction of novel genes not previously associated with intestinal iron transport. The Menkes copper ATPase (ATP7a) and metallothionein were strongly induced at all ages studied, suggesting increased copper absorption by enterocytes during iron deficiency. We also found significantly increased liver copper levels in 7- to 12-wk-old iron-deficient rats. Also upregulated at most ages examined were the sodium-dependent vitamin C transporter, tripartite motif protein 27, aquaporin 4, lipocalin-interacting membrane receptor, and the breast cancer-resistance protein (ABCG2). Some genes also showed decreased expression with iron deprivation, including several membrane transporters, metabolic enzymes, and genes involved in the oxidative stress response. We speculate that dietary iron deprivation leads to increased intestinal copper absorption via DMT1 on the brush-border membrane and the Menkes copper ATPase on the basolateral membrane. These findings may thus explain copper loading in the iron-deficient state. We also demonstrate that many other novel genes may be differentially regulated in the setting of iron deprivation.

scholarly journals Measuring Reticulocyte Hemoglobin Content As a Marker for Iron Deficiency and Response to Therapy Represents a Paradigm Shift in Care

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 42-43
Author(s):  
Michael Auerbach ◽  
Carlo Brugnara ◽  
Steve Staffa
Keyword(s):  
Iron Deficiency ◽  
Serum Ferritin ◽  
Biochemical Markers ◽  
Roc Analysis ◽  
Transferrin Saturation ◽  
Iron Administration ◽  
Iron Deficient ◽  
Ferritin Iron ◽  
Iv Iron ◽  
Iron Replacement

It is estimated anemia affects over 30% of the world's population, with iron deficiency (ID) the overwhelmingly most common cause. Whether absolute due to blood loss and/or iron sequestration to underlying morbidity, the need for repletion especially in females, is a formidable medical issue. The diagnosis of iron deficient erythropoiesis has been traditionally based on the biochemical parameters ferritin and percent transferrin saturation (TSAT), mean cell volume and hemoglobin (Hb) concentration. In recent years, reticulocyte Hb content has emerged as a parameter helpful in identifying iron deficient erythropoiesis and informing a need, or lack thereof, for replacement. 556 consecutive, non-selected patients referred for diagnosis and/or treatment of anemia were included in this diagnostic study to compare the performance of reticulocyte hemoglobin equivalent (RET-He) versus traditional biochemical markers for diagnosis and treatment of IDA. CBC, serum ferritin, iron and TSAT were performed as clinically indicated. RET-He was measured with a Sysmex XN-450 analyzer on the residual CBC sample. 556 patients were studied at baseline and 150 were subsequently treated with intravenous (IV) iron. 240/556 were seen at follow-up, with 57 treated and 183 not treated with IV iron. At baseline, ret-He, positively correlated with Hb (Spearman correlation (rho)=0.365, P &lt; 0.001), MCV (rho=0.576, P &lt; 0.001), MCH (rho=0.777, P &lt; 0.001), serum iron (rho=0.526, P &lt; 0.001) and TSAT (rho=0.492, P &lt; 0.001). Serum iron, and TSAT (but not serum ferritin or MCV, or absolute reticulocyte count) positively correlated with Hb concentrations. Based on either a serum ferritin &lt;30 ng/ml and/or a TSAT&lt; 20%, 241/556 (43.4%) patients were diagnosed as iron deficient. Anemia was present in 64/241 of the iron deficient patients (26.6%). Despite the limitations of the biochemical markers outlined above, we performed ROC analysis assessing the value of RET-He in identifying iron deficiency as defined by serum ferritin &lt;30 ng/mL or transferrin saturation &lt;20%. ROC analysis demonstrates a reasonable performance for RET-He (AUC= 0.733, 95% CI: 0.692, 0.775), with a cut-off value of &lt;30.7 pg yielding 68.2% sensitivity and 69.7% specificity. Using both Hb and RET-He in a multivariable ROC analysis does not provide an improved AUC, as compared to just using RET-He (AUC=0.605 vs.0.733). IV iron administration was associated with significant increases in Hb, MCV, MCH, RET-He, serum ferritin, iron and TSAT, whereas in the no-IV iron cohort, there was a small reduction in RET-He and small increases in MCV and MCH, with no significant variations in Hb and in the other parameters. Serum ferritin was below 30 ng/mL in 18/57 (32%) of the patients requiring IV iron and in 19/183 (10.4%) of those not requiring iron at visit 1. These values changed to 4/57 (7%) (P=0.002) and 23/183 (13%) (P=0.623) at visit 2, respectively. Regression analysis for Hb response following IV iron showed that baseline RET-He values are predictive of Hb response, with every unitary increase in RET-He corresponding to a blunting of the Hb change by -0.19 g/dl (95% CI: -0.27, -0.11; P &lt; 0.001). Changes in RE-He associated with IV iron administration are also predictive of the Hb response, with every additional unit increase in RET-He corresponding to a 0.21 g/dL increase in Hb (95% CI: 0.13, 0.28; P &lt; 0.009). ROC analysis for the capability to predict Hb response among the 57 patients receiving IV iron shows that a value of baseline RET-He &lt; 28.5 pg together with a baseline Hb value &lt; 10.3 g/dL provide the highest Youden's index for predicting Hb response &gt; 1.0 g/dl, with sensitivity of 84% and specificity of 78%. The Figure presents data for the 21/57 patients who had RET-He &lt; 28.5 pg and Hb &lt; 10.3 g/dL vs the 36/57 who did not. The present data show that an abnormally low ret-He value (&lt; 28.5 pg) identifies patients who will respond to iron replacement, obviating delays to obtain standard iron parameters. Baseline and changes in ret-He also associate with Hb response. Given the enormous prevalence of ID in the general population the use of the ret-He, which is available with the CBC on the autoanalyzer, informs need for iron replacement, or lack thereof, represents an increase in convenience for patient and physician, decreases costs, streamlines care and represents an improvement in the treatment paradigm of one of the commonest maladies on the planet. Figure 1 Disclosures Auerbach: AMAG: Research Funding; Sysmex: Research Funding. Brugnara:American Journal of Hematology: Other; Sysmex America Inc.: Consultancy.

scholarly journals Standardization & Development of Rat Model with Iron Deficiency Anaemia Utilising Commercial Available Iron Deficient Food

2019 ◽  
Vol 16 (1) ◽  
pp. 71-77
Author(s):  
Mansee Kapil Thakur ◽  
Smital Sameer Kulkarni ◽  
Nimain Mohanty ◽  
Nitin. N. Kadam ◽  
Niharika S. Swain
Keyword(s):  
Iron Deficiency ◽  
Rat Model ◽  
Iron Deficiency Anaemia ◽  
Test Group ◽  
Peripheral Smear ◽  
Deficient Diet ◽  
Deficiency Anaemia ◽  
Iron Deficient ◽  
Body Weights ◽  
Before And After

Many research centres have developed various animal models with Iron Deficiency Anaemia (IDA) by using iron deficient feeds as well as different chemicals. Model for iron deficiency anaemia (IDA) in rats has been created by the use of iron elimination from diet components as much as possible. The present study elaborates and concludes the development of IDA rat model by investigating different parameters like body weight, haematological indices, peripheral smear, immunoassay studies and histopathological studies using commercially available iron deficient diet. 12 Wistar albino female rats weighing 180-200 gm were selected with normal haemoglobin range of 12 - 15 g/dL purchased from Bombay Veterinary College, Parel and divided into two groups – Control (3 no. of rats) and Test (9 no. of rats). The test group was fed with iron deficient diet (VRK Nutritional Solutions) whereas control group was fed with standard diet. The time duration of the study was 5 weeks (35 days) and 6 weeks (42 days). Retro orbital blood for both control and treated was drawn at both time intervals so as to analyse haematological and immunoassay studies. Peripheral smear staining was carried out to observe the gross morphology of RBCs for iron deficient and control rats. The body weights were recorded before and after treatment and statistical significance was calculated. Post exposure rats were dissected and organs like heart, kidney, liver, lungs and spleen were collected for histopathological analysis. Our results showed decreased levels of hemoglobin (Hb), hematocrit (HCT), mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), reticulocyte count, serum iron (SI), serum ferritin (SF) and an increase in total iron binding capacity (TIBC). in IDA animals exposed to 42 days of iron deficient diet. Significant difference (p<0.5) was observed in body weights of rats when compared with the data before and after treatment. The peripheral smear has indicated microcytic hypochromic RBCs in test group confirming development of IDA model. The histopathological results revealed the abnormality at cellular level like congestion of blood vessels in heart, congestion and centrilobular hepatocyte with inflammatory cell infiltration in liver, perivasculitis in lungs and decrease in white pulp in spleen whereas kidney were found normal. Our results clearly demonstrate iron deficient rat model when administered with IDA feed. This model can be used for estimation of efficiency of new food products and food supplements enriched with iron.

Dietary iron-deficient anemia induces a variety of metabolic changes and even apoptosis in rat liver: a DNA microarray study

2010 ◽  
Vol 42 (2) ◽  
pp. 149-156 ◽  
Author(s):  
Asuka Kamei ◽  
Yuki Watanabe ◽  
Tomoko Ishijima ◽  
Mariko Uehara ◽  
Soichi Arai ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Iron Deficiency ◽  
Dna Microarray ◽  
Global Analysis ◽  
Control Diet ◽  
Diet Group ◽  
Iron Level ◽  
Dietary Iron ◽  
Deficient Diet ◽  
Iron Deficient

Anemia can be induced by dietary iron deficiency, as well as by hemorrhagia. It may also be associated with changes in lipid metabolism. However, no global analysis detailing the consequences of iron deficiency in the liver has yet been conducted. Since the liver is a metabolically important organ and also a major iron-storing organ, we performed a comprehensive transcriptome analysis to determine the effects of iron deficiency on hepatic gene expression. Four-week-old rats were fed an iron-deficient diet, ∼3 ppm iron, ad libitum for 16 days. These rats were compared with similar rats pair-fed a control diet with a normal iron level, 48 ppm iron. The 16-day iron-deficient diet apparently induced anemia. On day 17, the rats were killed under anesthesia, and their livers were dissected for DNA microarray analysis. We identified 600 upregulated and 500 downregulated probe sets that characterized the iron-deficient diet group. In the upregulated probe sets, genes involved in cholesterol, amino acid, and glucose metabolism were significantly enriched, while genes related to lipid metabolism were significantly enriched in the downregulated probe sets. We also found that genes for caspases 3 and 12, which mediate endoplasmic reticulum (ER)-specific apoptosis, were upregulated in the iron-deficient group. Combined, these results suggest that iron deficiency exerts various influences, not only on nutrient metabolism but also on apoptosis, as a consequence of ER stress in the liver.

Histological Evaluation of Megakaryocytes and Angiogenic Signaling Molecules of Bone Marrow in Experimentally Induced Iron Deficiency Anemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 953-953
Author(s):  
Jessica Garcia ◽  
Peggy Mankin ◽  
Pedro De Alarcon
Keyword(s):  
Bone Marrow ◽  
Iron Deficiency ◽  
Factor Viii ◽  
Iron Deficiency Anemia ◽  
Plasma Levels ◽  
Signaling Molecules ◽  
Histological Evaluation ◽  
Deficiency Anemia ◽  
Deficient Diet ◽  
Iron Deficient

Abstract Iron deficiency Anemia (IDA) induced reactive thrombocytosis occurs in children. The mechanisms involved in this phenomenon are indeterminate. Traditional cytokines involved in megakaryopoiesis such as Thrombopoietin (TPO), IL-6, and IL-11 have not been shown to be associated with this IDA induced thrombocytosis. Recent studies suggest that growth factors and signaling molecules involved in angiogenesis influence the proliferation and/or differentiation of megakaryocytes. A recent study observed that VEGFR1-mediated pathway up-regulates CXCR4 on megakaryocytes, leading to enhanced platelet production via distribution of megakaryocytes. We previously reported a statistically increased serum/plasma levels of FLT-3 and PDGF, but did not find an increase in plasma levels of TPO, VEGF and CXCR4 in an experimentally induced IDA in rats, when compared to control rats. We now present the histological evaluation of megakaryocytes and the expression of angiogenic signaling molecules, VEGF and CXCR4, in bone marrows of control and IDA rats. Six week old male Sprague-Dawley rats with jugular vein cannulas were obtained. Diet for control rats (N=9) and iron deficient diet rats (N=18) had 50 ppm and 7-8 ppm iron in Purina chow respectively. CBC, Iron Panel, and cytokines were drawn at baseline and five weeks later. On day 0, 1.5 mL of blood was drawn from iron deficient diet rats to further induce anemia. Rats were euthanized by CO2 asphyxiation and cardiac puncture. Femurs were collected, decalcified, and embedded in paraffin. Thin sliced sections were obtained to make slides. The slides were stained with hematoxylin and eosin (H&E), and with peroxidase linked anti factor VIII, VEGF, and CXCR4 according to manufacturer's instructions. The slides were evaluated under 40x microscopy. An area of 0.1 mm2 was selected and the numbers of megakaryocytes in the selected area were visually quantitated. Immunoperoxidase stained slides were analyzed using Image J software. When reviewing H&E stained bone marrow slides per 0.1 mm2, control rats contained 4 megakaryocytes, while those from IDA rats contained 11 megakaryocytes (P=0.0001). In Factor VIII stained slides, quantitative analysis of peroxidase stained megakaryocytes in control group contained 49,271 pixels, while staining in the IDA rats was 185,076 pixels (P=0.00002). When the analysis was carried out looking at vessel staining, there was a significant difference between controls (3.6) and IDA (8.5) per 0.1 mm2 (P=0.00001). In the VEGF stained slides, visual analysis of peroxidase stain showed increased intensity of staining per cell in the IDA rats. In the CXCR4 stained slides, visual inspection of the control bone marrows showed a rare small round cell weakly stained while these cells were more frequent and strongly stained in IDA rats. We successfully induced IDA in an animal model with coexisting thrombocytosis. Bone marrow slides in IDA rats documented the expected increase in number of megakaryocytes. In addition, we documented a marked increase in vascular structures of IDA rats. Contrary to our previously reported plasma levels, VEGF intensity of stain was greater within IDA rat megakaryocytes when compared to control rat megakaryocytes. We also documented an increase of CXCR4 in the bone marrows of IDA rats. However, this increase was limited to early stage megakaryocyte development cells suggesting a role during the differentiation process of megakaryocytes. Both our previous report on circulating angiogenic signaling molecules and the current histological data suggest an important role for angiogenesis in the development of IDA induced thrombocytosis. Disclosures No relevant conflicts of interest to declare.

scholarly journals Gastrin-Deficient Mice Have Disturbed Hematopoiesis in Response to Iron Deficiency

Endocrinology ◽  
2011 ◽  
Vol 152 (8) ◽  
pp. 3062-3073 ◽  
Author(s):  
Suzana Kovac ◽  
Gregory J. Anderson ◽  
Warren S. Alexander ◽  
Arthur Shulkes ◽  
Graham S. Baldwin
Keyword(s):  
Iron Deficiency ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Iron Homeostasis ◽  
Transferrin Saturation ◽  
Deficient Diet ◽  
Direct Role ◽  
Iron Deficient

Gastrins are peptide hormones important for gastric acid secretion and growth of the gastrointestinal mucosa. We have previously demonstrated that ferric ions bind to gastrins, that the gastrin-ferric ion complex interacts with the iron transport protein transferrin in vitro, and that circulating gastrin concentrations positively correlate with transferrin saturation in vivo. Here we report the effect of long-term dietary iron modification on gastrin-deficient (Gas−/−) and hypergastrinemic cholecystokinin receptor 2-deficient (Cck2r−/−) mice, both of which have reduced basal gastric acid secretion. Iron homeostasis in both strains appeared normal unless the animals were challenged by iron deficiency. When fed an iron-deficient diet, Gas−/− mice, but not Cck2r−/−mice, developed severe anemia. In iron-deficient Gas−/−mice, massive splenomegaly was also apparent with an increased number of splenic megakaryocytes accompanied by thrombocytosis. The expression of the mRNA encoding the iron-regulatory peptide hepcidin, Hamp, was down-regulated in both Cck2r−/− and Gas−/−mice on a low-iron diet, but, interestingly, the reduction was greater in Cck2r−/− mice and smaller in Gas−/− mice than in the corresponding wild-type strains. These data suggest that gastrins play an important direct role, unrelated to their ability to stimulate acid secretion, in hematopoiesis under conditions of iron deficiency.

scholarly journals Maternal iron deficiency perturbs embryonic cardiovascular development

2020 ◽  
Author(s):  
Jacinta I. Kalisch-Smith ◽  
Nikita Ved ◽  
Dorota Szumska ◽  
Jacob Munro ◽  
Michael Troup ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Iron Deficiency ◽  
Mouse Model ◽  
Iron Deficiency Anaemia ◽  
Human Populations ◽  
Cardiovascular Development ◽  
Deficiency Anaemia ◽  
Iron Administration ◽  
Iron Deficient ◽  
Maternal Iron

AbstractCongenital heart disease (CHD) is the most common type of birth defect, with a global prevalence of 0.9% of live births1. Most research in the last 30 years has focused on finding genetic causes of CHD. However, despite the association of over 100 genes with CHD, mutations in these genes only explain ~30% of cases2. Many of the remaining cases of CHD are caused by in utero exposure to environmental factors3. Here we have identified a completely new environmental teratogen causing CHD: maternal iron deficiency. In humans, iron deficiency anaemia is a major global health problem. 38% of pregnant women worldwide are anaemic4, and at least half of these are due to iron deficiency, the most prevalent micronutrient deficiency. We describe a mouse model of maternal iron deficiency anaemia that causes severe cardiovascular defects in her offspring. We show that these defects likely arise from increased retinoic acid signalling in iron deficient embryos, probably due to reduced activity of the iron-dependent retinoic acid catabolic CYP26 enzymes. The defects can be prevented by maternal iron administration early in pregnancy, and are also greatly reduced in offspring of mothers deficient in both iron and the retinoic acid precursor vitamin A. Finally, one puzzling feature of many genetic forms of CHD in humans is the considerable variation in penetrance and severity of defects. We show that maternal iron deficiency acts as a significant modifier of heart and craniofacial phenotype in a mouse model of Down syndrome. Given the high incidence of maternal iron deficiency, peri-conceptional iron monitoring and supplementation could be a viable strategy to reduce the prevalence and severity of CHD in human populations worldwide.

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