Ronco A M, Urrutia M, Montenegro M, Llanos M N
Laboratory of Nutrition and Metabolic Regulation, Institute of Nutrition and Food Technology, INTA, University of Chile, Casilla 138-11, Santiago, Chile.
Toxicol Lett. 2009 Aug 10;188(3):186-91. doi: 10.1016/j.toxlet.2009.04.008. Epub 2009 Apr 18.
Cadmium exposure induces low birth weight through unknown mechanisms. Since low birth weight is associated to foetal exposure to high glucocorticoids (GC) concentrations, we hypothesized that low birth weight induced by prenatal exposure to Cd(2+) is, at least in part, mediated by higher foetal exposure to GC, specifically corticosterone, the main active GC in rodents. Pregnant rats were exposed to different dose of CdCl(2) administered in drinking water during the whole pregnancy period. At term, corticosterone was measured by enzyme immunoassay in maternal and foetal blood and in placental tissues. Cadmium was determined in placentas, maternal tissues (liver and kidney) and foetuses by inductively coupled plasma-mass spectrometry (ICP-MS). Placental 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity and expression were determined by a radiometric conversion assay and quantitative RT-PCR respectively. Results demonstrated that 50 ppm of Cd(2+), which was accumulated in different maternal tissues but not in the foetus, reduced pup birth weights and increased plasma corticosterone concentrations, both in mother and foetus. Placental 11beta-HSD2 activity and expression did not change by the treatment. We conclude that 50 ppm of Cd(2+) administered during pregnancy, increase foetal corticosterone concentrations due, probably, to alterations of the regulatory mechanisms of placental barrier to GC causing a mild but significant reduced birth weight.
镉暴露通过未知机制导致低出生体重。由于低出生体重与胎儿暴露于高浓度糖皮质激素（GC）有关，我们推测产前暴露于Cd(2+)所导致的低出生体重至少部分是由胎儿更高水平地暴露于GC介导的，特别是皮质酮，它是啮齿动物体内主要的活性GC。在整个孕期，给怀孕大鼠饮用含不同剂量CdCl(2)的水。足月时，通过酶免疫测定法测量母体和胎儿血液以及胎盘组织中的皮质酮。通过电感耦合等离子体质谱法（ICP-MS）测定胎盘、母体组织（肝脏和肾脏）以及胎儿中的镉含量。分别通过放射性转化测定法和定量RT-PCR测定胎盘II型11β-羟基类固醇脱氢酶（11β-HSD2）的活性和表达。结果表明，50 ppm的Cd(2+)在不同母体组织中蓄积，但未在胎儿中蓄积，它降低了幼崽出生体重，并增加了母体和胎儿血浆皮质酮浓度。处理后胎盘11β-HSD2的活性和表达没有变化。我们得出结论，孕期给予50 ppm的Cd(2+)会增加胎儿皮质酮浓度，这可能是由于胎盘对GC的屏障调节机制发生改变，导致出生体重出现轻度但显著的降低。
