Effect of postnatal exposure to benzo[a]pyrene on the uterus of immature rats.
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.
Kummer
Vladimír
V
Veterinary Research Institute, Brno, Czech Republic.
Masková
Jarmila
J
Zralý
Zdenek
Z
Matiasovic
Ján
J
Faldyna
Martin
M
D000818:Animals; D000831:Animals, Newborn; D001564:Benzo(a)pyrene / Q000633:toxicity*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D004965:Estrogen Antagonists / Q000633:toxicity*; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology; D004997:Ethinyl Estradiol / Q000494:pharmacology; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D007124:Immunoenzyme Techniques; D007279:Injections, Subcutaneous; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012741:Sexual Maturation; D014599:Uterus / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology
D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D004967:Estrogens; D001564:Benzo(a)pyrene; D004997:Ethinyl Estradiol