scholarly journals Dietary-induced gestational iron deficiency inhibits postnatal tissue iron delivery and postpones the cessation of active nephrogenesis in rats

2017 ◽  
Vol 29 (5) ◽  
pp. 855 ◽  
Author(s):  
Mary Y. Sun ◽  
Joseph C. Woolley ◽  
Sharon E. Blohowiak ◽  
Zachary R. Smith ◽  
Ashajyothi M. Siddappa ◽  
...  

Gestational iron deficiency (ID) can alter developmental programming through impaired nephron endowment, leading to adult hypertension, but nephrogenesis is unstudied. Iron status and renal development during dietary-induced gestational ID (<6 mg Fe kg–1 diet from Gestational Day 2 to Postnatal Day (PND) 7) were compared with control rats (198 mg Fe kg–1 diet). On PND2–PND10, PND15, PND30 and PND45, blood and tissue iron status were assessed. Nephrogenic zone maturation (PND2–PND10), radial glomerular counts (RGCs), glomerular size density and total planar surface area (PND15 and PND30) were also assessed. Blood pressure (BP) was measured in offspring. ID rats were smaller, exhibiting lower erythrocyte and tissue iron than control rats (PND2–PND10), but these parameters returned to control values by PND30–PND45. Relative kidney iron (µg g–1 wet weight) at PND2-PND10 was directly related to transport iron measures. In ID rats, the maturation of the active nephrogenic zone was later than control. RGCs, glomerular size, glomerular density, and glomerular planar surface area were lower than control at PND15, but returned to control by PND30. After weaning, the kidney weight/rat weight ratio (mg g–1) was heavier in ID than control rats. BP readings at PND45 were lower in ID than control rats. Altered kidney maturation and renal adaptations may contribute to glomerular size, early hyperfiltration and long-term renal function.

Blood ◽  
1990 ◽  
Vol 75 (9) ◽  
pp. 1870-1876 ◽  
Author(s):  
BS Skikne ◽  
CH Flowers ◽  
JD Cook

Abstract This study was undertaken to evaluate the role of serum transferrin receptor measurements in the assessment of iron status. Repeated phlebotomies were performed in 14 normal volunteer subjects to obtain varying degrees of iron deficiency. Serial measurements of serum iron, total iron-binding capacity, mean cell volume (MCV), free erythrocyte protoporphyrin (FEP), red cell mean index, serum ferritin, and serum transferrin receptor were performed throughout the phlebotomy program. There was no change in receptor levels during the phase of storage iron depletion. When the serum ferritin level reached subnormal values there was an increase in serum receptor levels, which continued throughout the phlebotomy program. Functional iron deficiency was defined as a reduction in body iron beyond the point of depleted iron stores. The serum receptor level was a more sensitive and reliable guide to the degree of functional iron deficiency than either the FEP or MCV. Our studies indicate that the serum receptor measurement is of particular value in identifying mild iron deficiency of recent onset. The iron status of a population can be fully assessed by using serum ferritin as a measure of iron stores, serum receptor as a measure of mild tissue iron deficiency, and hemoglobin concentration as a measure of advanced iron deficiency.


Blood ◽  
2003 ◽  
Vol 101 (9) ◽  
pp. 3359-3363 ◽  
Author(s):  
James D. Cook ◽  
Carol H. Flowers ◽  
Barry S. Skikne

Current initiatives to reduce the high prevalence of nutritional iron deficiency have highlighted the need for reliable epidemiologic methods to assess iron status. The present report describes a method for estimating body iron based on the ratio of the serum transferrin receptor to serum ferritin. Analysis showed a single normal distribution of body iron stores in US men aged 20 to 65 years (mean ± 1 SD, 9.82 ± 2.82 mg/kg). A single normal distribution was also observed in pregnant Jamaican women (mean ± 1 SD, 0.09 ± 4.48 mg/kg). Distribution analysis in US women aged 20 to 45 years indicated 2 populations; 93% of women had body iron stores averaging 5.5 ± 3.35 mg/kg (mean ± 1 SD), whereas the remaining 7% of women had a mean tissue iron deficit of 3.87 ± 3.23 mg/kg. Calculations of body iron in trials of iron supplementation in Jamaica and iron fortification in Vietnam demonstrated that the method can be used to calculate absorption of the added iron. Quantitative estimates of body iron greatly enhance the evaluation of iron status and the sensitivity of iron intervention trials in populations in which inflammation is uncommon or has been excluded by laboratory screening. The method is useful clinically for monitoring iron status in those who are highly susceptible to iron deficiency.


2011 ◽  
Vol 300 (3) ◽  
pp. G470-G476 ◽  
Author(s):  
Narasimha V. Hegde ◽  
Erica L. Unger ◽  
Gordon L. Jensen ◽  
Pamela A. Hankey ◽  
Robert F. Paulson

Dietary iron is particularly critical during periods of rapid growth such as in neonatal development. Human and rodent studies have indicated that iron deficiency or excess during this critical stage of development can have significant long- and short-term consequences. Since the requirement for iron changes during development, the availability of adequate iron is critical for the differentiation and maturation of individual organs participating in iron homeostasis. We have examined in rats the effects of dietary iron supplement following neonatal iron deficiency on tissue iron status in relation to erythropoietic ability during 16 wk of postweaning development. This physiological model indicates that postweaning iron-adequate diet following neonatal iron deficiency adversely affects erythroid differentiation in the bone marrow and promotes splenic erythropoiesis leading to splenomegaly and erythrocytosis. This altered physiology of iron homeostasis during postweaning development is also reflected in the inability to maintain liver and spleen iron concentrations and the altered expression of iron regulatory proteins in the liver. These studies provide critical insights into the consequences of neonatal iron deficiency and the dietary iron-induced cellular signals affecting iron homeostasis during early development.


1988 ◽  
Vol 255 (2) ◽  
pp. R326-R331
Author(s):  
T. Intragumtornchai ◽  
H. A. Huebers ◽  
M. Eng ◽  
C. A. Finch

Quantitative measurements of transferrin receptors, tissue transferrin, tissue iron uptake, and erythroid cellularity have been carried out in rats with altered erythropoiesis and altered iron balance. Erythroid receptors increased with erythroid hyperplasia, with the increase in proportion to the increased number of red cell precursors in phenylhydrazine-treated rats. Receptors increased disproportionately in iron deficiency due to both erythroid hyperplasia and an increase in receptors in the individual cell. There was a ratio of 1:1 between cell-related transferrin and receptors in circulating reticulocytes but a disproportionate amount of cell-related transferrin in fixed erythroid tissues (marrow and spleen), suggesting that there was some other reason for the concentration of transferrin in these tissues. Erythron iron uptake was increased in proportion to the increased receptor number in phenylhydrazine-treated animals but was reduced in iron deficiency because of the limited amount of iron-bearing transferrin. These studies demonstrate the dominant role of erythron cellularity and iron status in vivo in determining total receptor number and the importance of receptor number and iron supply in tissue iron uptake.


1986 ◽  
Vol 250 (2) ◽  
pp. F348-F356 ◽  
Author(s):  
L. A. Scharschmidt ◽  
J. G. Douglas ◽  
M. J. Dunn

We examined the possibility that glomerular prostaglandin E2 (PGE2) regulates the action of angiotensin II (ANG II) on mesangial contraction and filtration surface area. Using isolated rat glomeruli we indirectly assessed mesangial contraction and filtration surface area through measurements of glomerular planar surface area (GPSA) by image-analysis microscopy. ANG II reduced GPSA by approximately 20% in human and rat glomeruli, with threshold concentrations of 1 X 10(-13) M and maximum effect at 5 X 10(-11) M ANG II. Inhibition of glomerular PG synthesis with indomethacin or meclofenamate potentiated the threshold response of ANG II to reduce GPSA. Arachidonic acid (5 micrograms/ml) blunted both the threshold and the maximum responses of GPSA to ANG II. PGE2, 10(-8) and 10(-9) M, also decreased glomerular contraction to ANG II. Endoperoxide (EP) analogues decreased GPSA and EP 045, a thromboxane A2 (TXA2) receptor blocker, eliminated the contractile responses of glomeruli to the EP analogues. Authentic TXA2, synthesized from sheep platelet microsomes, also reduced GPSA. We conclude that glomerular products of arachidonate cyclooxygenation may either relax or contract the mesangium, thereby preserving or reducing filtration surface area. PGE2 exerts protective actions to reduce the mesangial contraction of ANG II, primarily through postreceptor effects. TXA2 may decrease glomerular filtration rate in certain diseases through direct actions on the mesangium.


Blood ◽  
1990 ◽  
Vol 75 (9) ◽  
pp. 1870-1876 ◽  
Author(s):  
BS Skikne ◽  
CH Flowers ◽  
JD Cook

This study was undertaken to evaluate the role of serum transferrin receptor measurements in the assessment of iron status. Repeated phlebotomies were performed in 14 normal volunteer subjects to obtain varying degrees of iron deficiency. Serial measurements of serum iron, total iron-binding capacity, mean cell volume (MCV), free erythrocyte protoporphyrin (FEP), red cell mean index, serum ferritin, and serum transferrin receptor were performed throughout the phlebotomy program. There was no change in receptor levels during the phase of storage iron depletion. When the serum ferritin level reached subnormal values there was an increase in serum receptor levels, which continued throughout the phlebotomy program. Functional iron deficiency was defined as a reduction in body iron beyond the point of depleted iron stores. The serum receptor level was a more sensitive and reliable guide to the degree of functional iron deficiency than either the FEP or MCV. Our studies indicate that the serum receptor measurement is of particular value in identifying mild iron deficiency of recent onset. The iron status of a population can be fully assessed by using serum ferritin as a measure of iron stores, serum receptor as a measure of mild tissue iron deficiency, and hemoglobin concentration as a measure of advanced iron deficiency.


1994 ◽  
Vol 130 (2) ◽  
pp. 261-263 ◽  
Author(s):  
M.I. White ◽  
J. Currie ◽  
M.P. Williams

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2221
Author(s):  
Hugo G. Quezada-Pinedo ◽  
Florian Cassel ◽  
Liesbeth Duijts ◽  
Martina U. Muckenthaler ◽  
Max Gassmann ◽  
...  

In pregnancy, iron deficiency and iron overload increase the risk for adverse pregnancy outcomes, but the effects of maternal iron status on long-term child health are poorly understood. The aim of the study was to systematically review and analyze the literature on maternal iron status in pregnancy and long-term outcomes in the offspring after birth. We report a systematic review on maternal iron status during pregnancy in relation to child health outcomes after birth, from database inception until 21 January 2021, with methodological quality rating (Newcastle-Ottawa tool) and random-effect meta-analysis. (PROSPERO, CRD42020162202). The search identified 8139 studies, of which 44 were included, describing 12,7849 mother–child pairs. Heterogeneity amongst the studies was strong. Methodological quality was predominantly moderate to high. Iron status was measured usually late in pregnancy. The majority of studies compared categories based on maternal ferritin, however, definitions of iron deficiency differed across studies. The follow-up period was predominantly limited to infancy. Fifteen studies reported outcomes on child iron status or hemoglobin, 20 on neurodevelopmental outcomes, and the remainder on a variety of other outcomes. In half of the studies, low maternal iron status or iron deficiency was associated with adverse outcomes in children. Meta-analyses showed an association of maternal ferritin with child soluble transferrin receptor concentrations, though child ferritin, transferrin saturation, or hemoglobin values showed no consistent association. Studies on maternal iron status above normal, or iron excess, suggest deleterious effects on infant growth, cognition, and childhood Type 1 diabetes. Maternal iron status in pregnancy was not consistently associated with child iron status after birth. The very heterogeneous set of studies suggests detrimental effects of iron deficiency, and possibly also of overload, on other outcomes including child neurodevelopment. Studies are needed to determine clinically meaningful definitions of iron deficiency and overload in pregnancy.


2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Daniela Meiser ◽  
Lale Kayikci ◽  
Matthias Orth

AbstractObjectivesDiagnosing disturbances in iron metabolism can be challenging when accompanied by inflammation. New diagnostic tools such as the “Thomas-plot” (TP) (relation of soluble transferrin receptor [sTfR]/log ferritin to reticulocyte hemoglobin content [RET-He]) were established to improve classification of anemias. Aim of this retrospective study was to assess the added diagnostic value of the TP in anemia work up.MethodsPatients from December 2016 to September 2018 with a complete blood count, iron status, RET-He and sTfR were manually classified into the four quadrants of the TP on basis of conventional iron markers. Manual and algorithm-based classifications were compared using cross tabulations, Box–Whisker-Plots as well as Receiver-Operating-Characteristics (ROC) to calculate the diagnostic accuracy using Area under the Curve (AUC) analysis.ResultsA total of 3,745 patients with a conventional iron status, including 1,721 TPs, could be evaluated. In 70% of the cases the manual classification was identical to the TP, in 10% it was deviant. 20% could not clearly be classified, mostly due to inflammatory conditions. In the absence of an inflammatory condition, ferritin was a reliable parameter to define iron deficiency (ID) (AUC 0.958). In the presence of inflammation, the significance of the ferritin index (AUC 0.917) and of the RET-He (AUC 0.957) increased.ConclusionsThe TP can be useful for narrowing down the causes of anemia in complex cases. Further studies with focus on special patient groups, e.g., oncological or rheumatic patients, are desirable.


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