Ovarian disorders in immature rats after postnatal exposure to environmental polycyclic aromatic hydrocarbons.

The study investigated the effects of postnatal exposure to polycyclic aromatic hydrocarbons (PAHs) on the development of the rat ovary. Neonates were injected on each postnatal day 1-14 with benzo(a)pyrene (BaP), benz(a)anthracene (BaA) and benzo(k)fluoranthene (BkF) (0.1, 1.0, 5.0 or 10.0 mg kg(-1)), ethynylestradiol (EE; 1.0 µg kg(-1)) or a vehicle (control group). The rats were killed on day 23. Postnatal exposure to BaP increased the total number of antral follicles in ovaries (P < 0.05) and the number of nonatretic follicles (P < 0.01) as a result of a lower degree of apoptosis of granulosa cells, and the thickness of theca cell layers (P < 0.01). Similar histological findings were observed after BaA administration. Conversely, BkF exposure caused a decrease in the number of antral follicles, but did not alter the other investigated parameters. Degeneration of primordial oocytes after exposure to PAHs was observed only after exposure to BaP. Treatment with BaP at doses of 1.0 and 10.0 mg kg(-1) impaired 28.1 and 60.3% of the primordial follicles, respectively. Substantial alterations in ovarian ERß expression were detected in the rats; their intensity differed with the type of PAH. Response of the ovaries to EE (three injections of 1.0 µg kg(-1) on postnatal days 20-22) in rats exposed to PAHs was suppressed in contrast to the controls. The study showed that postnatal exposure to BaP, BaA and BkF altered ovarian ERß expression, disturbed morphological development of the ovaries and caused ovarian dysfunction in immature rats.

Estrogenic activity of environmental polycyclic aromatic hydrocarbons in uterus of immature Wistar rats.

Polycyclic aromatic hydrocarbons (PAHs) are an important group of environmental pollutants, known for their mutagenic and carcinogenic activities. Many PAHs are aryl hydrocarbon receptor (AhR) ligands and several recent studies have suggested that PAHs or their metabolites may activate estrogen receptors (ER). The present study investigated possible estrogenic/antiestrogenic effects of abundant environmental contaminants benzo[a]pyrene (BaP), benz[a]anthracene (BaA), fluoranthene (Fla) and benzo[k]fluoranthene (BkF) in vivo, using the immature rat uterotrophic assay. The present results suggest that BaA, BaP and Fla behaved as estrogen-like compounds in immature Wistar rats, when applied for 3 consecutive days at 10mg/kg/day, as documented by a significant increase of uterine weight and hypertrophy of luminal epithelium. These effects were likely to be mediated by ERalpha, a major subtype of ER present in uterus, as they were inhibited by treatment with ER antagonist ICI 182,780. BaA, the most potent of studied PAHs, induced a significant estrogenic effect within a concentration range 0.1-50mg/kg/day; however, it did not reach the maximum level induced by reference estrogens. The proposed antiestrogenicity of the potent AhR agonist BkF was not confirmed in the present in vivo study; the exposure to BkF did not significantly affect the uterine weight, although a weak suppression of ERalpha immunostaining was observed in luminal and glandular epithelium, possibly related to its AhR-mediated activity. The PAHs under study did not induce marked genotoxic damage in uterine tissues, as documented by the lack of Ser-15-phoshorylated p53 protein staining. With the exception of Fla, all three remaining compounds increased CYP1-dependent monooxygenation activities in liver at the doses used, suggesting that the potential tissue-specific antiestrogenic effects of PAHs mediated by metabolization of 17beta-estradiol also cannot be excluded. Taken together, these environmentally relevant PAHs induced estrogenic effects in vivo, which might affect their toxic impact and carcinogenicity.

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.