Leazer Tyra M, Liu Yaping, Klaassen Curtis D
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
Toxicol Appl Pharmacol. 2002 Nov 15;185(1):18-24. doi: 10.1006/taap.2002.9505.
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 (109)Cd-labeled CdCl(2) by oral gavage on gestation day (gd) 19. Tissues were collected on gd 20 for (109)Cd assessment (values expressed as pmol Cd). Greater accumulation of (109)Cd 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.
孕期肠道对必需营养素的吸收增加是其特征之一,因为母体胃肠道会经历生理和生化变化,以适应胎儿对必需营养素需求的增加。二价金属转运蛋白1(DMT-1)主要负责十二指肠对膳食铁的摄取,但也能识别镉(Cd)等非必需金属。与未怀孕小鼠相比,已报道怀孕小鼠对镉的吸收增加;然而,其机制尚不清楚。这项研究的目的是确定与未怀孕大鼠相比,怀孕大鼠对镉的吸收是否增加,以及这是否与DMT-1表达的时间依赖性上调相关。在妊娠第19天,对定时怀孕和未怀孕的雌性Sprague-Dawley大鼠经口灌胃给予(109)Cd标记的CdCl2。在妊娠第20天收集组织进行(109)Cd评估(数值以pmol镉表示)。在怀孕和未怀孕大鼠中,十二指肠中(109)Cd的积累均高于空肠和回肠。然而,怀孕大鼠小肠中的镉含量高于未怀孕大鼠。此外,怀孕大鼠肝脏和肾脏中积累的镉比未怀孕大鼠更多。用分支DNA信号扩增法测定十二指肠、胎盘、肝脏和肾脏中的DMT-1 mRNA水平。妊娠第21天怀孕大鼠十二指肠中的DMT-1 mRNA水平比未怀孕大鼠高约6倍,且怀孕大鼠的水平从妊娠第15天到第21天有所增加。在怀孕大鼠中观察到的镉吸收与DMT-1表达之间的相关性表明,DMT-1在孕期镉吸收增加中起作用。