Kummer Vladimír, Masková Jarmila, Zralý Zdenek, Matiasovic Ján, Faldyna Martin
Veterinary Research Institute, Brno, Czech Republic.
Exp Toxicol Pathol. 2007 Sep;59(1):69-76. doi: 10.1016/j.etp.2007.02.007. Epub 2007 Jun 20.
The objective of this study was to investigate the morphological effects of postnatal exposure to benzo[a]pyrene (B[a]P) on the development of the uterus, uterine estrogen receptor (ERalpha) expression, and the uterine response to estrogen stimulation using the uterotrophic bioassay in rats. Neonates were injected on each postnatal day (PND) 1-14 with B[a]P (0.1, 1.0 and 10.0mg/kg), ethynylestradiol (EE; 1.0 microg/kg) or vehicle (control group). All animals were killed on PND 23. Postnatal administration of B[a]P with doses of 1.0 and 10.0 mg/kg induced significant (P<0.01) reduction of uterine weight and significantly lowered (P<0.05) ERalpha expression in the luminal epithelium. The increase in uterine weight and luminal epithelium heights after EE stimulation (1.0 microg/kg) on PND 20-22 was significantly higher (P<0.01) in all groups in comparison with corresponding non-stimulated groups. However, the uterotrophic response in rats postnatally exposed to EE and B[a]P was significantly lower (P<0.01) than in controls. In the control and EE groups, EE stimulation on PND 20-22 induced a significant (P<0.01) decrease in ERalpha immunoreactivity of the luminal epithelium. In contrast, rats postnatally treated with B[a]P showed no change in the density of ERalpha immunostaining when detected after estrogenic stimulation. The present study showed that postnatal exposure to B[a]P caused pathological changes in constitution and maturation of uterine ERalpha resulting in disturbed morphological development and uterine dysfunction in immature rats.
本研究的目的是利用大鼠子宫增重生物测定法,研究出生后暴露于苯并[a]芘(B[a]P)对子宫发育、子宫雌激素受体(ERα)表达以及子宫对雌激素刺激反应的形态学影响。在出生后第1至14天,每天给新生大鼠注射B[a]P(0.1、1.0和10.0mg/kg)、乙炔雌二醇(EE;1.0μg/kg)或赋形剂(对照组)。所有动物在出生后第23天处死。出生后给予1.0和10.0mg/kg剂量的B[a]P可导致子宫重量显著降低(P<0.01),并使腔上皮中的ERα表达显著降低(P<0.05)。与相应的未刺激组相比,在出生后第20至22天给予EE刺激(1.0μg/kg)后,所有组的子宫重量和腔上皮高度增加均显著更高(P<0.01)。然而,出生后暴露于EE和B[a]P的大鼠的子宫增重反应显著低于对照组(P<0.01)。在对照组和EE组中,出生后第20至22天给予EE刺激可导致腔上皮的ERα免疫反应性显著降低(P<0.01)。相反,出生后用B[a]P处理的大鼠在雌激素刺激后检测时,ERα免疫染色密度没有变化。本研究表明,出生后暴露于B[a]P会导致子宫ERα的结构和成熟发生病理变化,从而导致未成熟大鼠的形态发育紊乱和子宫功能障碍。