Cadmium Absorption and Its Relationship to Divalent Metal Transporter-1 in the Pregnant Rat

doi:10.1006/taap.2002.9505

Toxicology and Applied Pharmacology

Volume 185, Issue 1, 15 November 2002, Pages 18-24

https://doi.org/10.1006/taap.2002.9505 Get rights and content

Abstract

Increased intestinal absorption of essential nutrients is characteristic of pregnancy as the maternal gastrointestinal tract undergoes physiological and biochemical changes to accommodate the increased demand for essential nutrients by the fetus. Divalent metal transporter-1 (DMT-1) is primarily responsible for dietary iron uptake in the duodenum but also recognizes nonessential metals such as cadmium (Cd). Increased absorption of Cd has been reported in pregnant compared with nonpregnant mice; however, the mechanism is not understood. The purpose of this work was to determine whether Cd absorption is increased in pregnant compared with nonpregnant rats and whether this correlates with a time-dependent up-regulation of DMT-1 expression. Timed pregnant and nonpregnant female Sprague–Dawley rats were administered ¹⁰⁹Cd-labeled CdCl₂ by oral gavage on gestation day (gd) 19. Tissues were collected on gd 20 for ¹⁰⁹Cd assessment (values expressed as pmol Cd). Greater accumulation of ¹⁰⁹Cd was observed in duodenum than in jejunum and ileum in both pregnant and nonpregnant rats. However, the amount of Cd in small intestine was higher in pregnant than nonpregnant rats. Additionally, more Cd accumulated in the liver and kidney of pregnant than nonpregnant rats. DMT-1 mRNA levels were determined in duodenum, placenta, liver, and kidney with branched DNA signal amplification. DMT-1 mRNA levels were about sixfold higher in duodenum of (gd 21) pregnant than nonpregnant rats and the levels in pregnant rats increased from gd 15 through gd 21. The correlation between Cd absorption and DMT-1 expression observed in pregnant rats suggests a role for DMT-1 in the increased absorption of Cd during pregnancy.

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Citation Excerpt :
Finally, increased Cd concentration was found in organs of pups whose mothers were exposed during gestation only (Jacquillet et al., 2007; Wang et al., 2016a) or gestation and lactation (Bekheet, 2011; Chemek et al., 2016). Cd exposure of pregnant females is of great concern because intestinal absorption is thought to be increased during this period in humans (Nishijo et al., 2004), but also in rodents (Leazer, 2002), leading to a higher amount of Cd entering the blood stream and possibly contaminating the fetus (Nishijo et al., 2004). The issue of progeny sensitivity to impairment of glucose homeostasis induced by contaminated mothers is important to tackle because, among the dramatically increased number of worldwide type II diabetes, a growing proportion involves young subjects.
Cadmium (Cd) is a metal which may participate in the development of type II diabetes even if Cd exposure levels are mild. However, experimental studies focusing on daily environmentally relevant doses are scarce, particularly for glucose metabolism of the offspring of chronically exposed mothers.
The aim is to measure the impact of maternal low level Cd exposure on glucose and lipid metabolism of offspring.
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^☆: Presented as a poster at the Society of Toxicology Meeting, Nashville, TN, March 17–21, 2002.

²: Present address: Nuclear Receptor Functional Analysis, Department of High Throughput Biology, GlaxoSmithKline, Research Triangle Park, NC 27709-3398

³: To whom all correspondence should be addressed. Fax (913) 588-7501; E-mail: [email protected]

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Regular ArticleCadmium Absorption and Its Relationship to Divalent Metal Transporter-1 in the Pregnant Rat☆

Abstract

Cadmium exposure in pregnancy and lactation in relation to iron status

Am. J. Public Health

Mechanism of zinc uptake by microvilli isolated from human term placenta

J. Cell. Physiol.

The teratogenicity of cadmium chloride in two stocks of Wistar rats

Teratology

Absorption of non-haem iron from food during normal pregnancy

Br. Med. J.

Two major pathways of zinc(II) acquisition by human placental syncytiotrophoblast

J. Cell. Physiol.

Bioavailabiity of orally administered cadmium and lead to the mother, fetus and neonate during pregnancy and lactation: An overview

Sci. Total Environ.

Gastrointestinal absorption of cadmium in mice during gestation and lactation. I. Short-term exposure studies

Toxicol. Appl. Pharmacol.

Gastrointestinal absorption of cadmium in mice during gestation and lactation. II. Continuous exposure studies

Toxicol. Appl. Pharmacol.

The surface area of the intestinal mucosa in the lactating rat

J. Physiol.

In vivo interactions of cadmium, copper, zinc and iron in the mouse and rat

J. Nutr.

Adaptation of the small intestine during pregnancy and lactation in the rat

Biochem. J.

Gastrointestinal hypertrophy in the lactating rat and its relation to food intake

J. Physiol.

Cellular and subcellular localization of the Nramp2 iron transporter in the intestinal brush border and regulation by dietary iron

Blood

Mobilization of hepatic cadmium in pregnant rats

Toxicol. Appl. Pharmacol.

Pregnancy-associated changes in plasma metallothionein concentration and renal cadmium accumulation in rats

Proc. Soc. Exp. Biol. Med.

Teratogenic effects of cadmium in rats

Teratology

Cellular localization of divalent metal transporter DMT-1 in rat kidney

Am. J. Physiol Renal Physiol.

Nramp2 is mutated in the anemic Belgrade (b) rat: Evidence of a role for Nramp2 in endosomal iron transport

Proc. Natl. Acad. Sci. USA

Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene

Nat. Genet.

Physiologic changes in pregnancy and their effect on drug disposition

Semin. Perinatol.

Effect of iron deficiency on placental transfer of iron and expression of iron transport proteins in vivo and in vitro

Biochem. J.

Identification and localization of divalent metal transporter-1 (DMT-1) in term human placenta

Placenta

Identification and characterization of a second mouse Nramp gene

Genomics

Iron-dependent regulation of the divalent metal ion transporter

FEBS Lett.

Cloning and characterization of a mammalian proton-coupled metal-ion transporter

Nature

Regular Article
Cadmium Absorption and Its Relationship to Divalent Metal Transporter-1 in the Pregnant Rat☆