In this study, a female pubertal assay on the effects of parabens, including methyl-, ethyl-, propyl-, isopropyl-, butyl-, and isobutylparaben, was performed in a female Sprague-Dawley rat model during the juvenile-peripubertal period. The rats were orally treated with these parabens from postnatal day 21-40 in a dose-dependent manner (62.5, 250 and 1000 mg/kg body weight [BW]/day). 17alpha-Ethinylestradiol (1mg/kg BW/day) was used as a positive control and corn oil as a vehicle. A high dose of methyl- and isopropylparaben (1000 mg/kg BW/day) resulted in a significant delay in the date of vaginal opening and a decrease in length of the estrous cycle. In measurements of organ weight and body weight, we observed significant weight changes in ovaries, adrenal glands, thyroid glands, liver, and kidneys; conversely, body weight was not altered following paraben treatment. The potential effects of parabens on estrogenicity were shown in histopathological abnormities in the reproductive organs. Histological analysis of the ovaries from the peripubertal rats revealed a decrease of corpora lutea, increase in the number of cystic follicles, and thinning of the follicular epithelium. In addition, morphological studies of the uterus revealed the myometrial hypertrophy by a high dose of propyl- and isopropylparaben (1000 mg/kg-day), and in all dose groups of butyl- and isobutylparabens. However, no significant histopathological changes were observed in the other organs (i.e. adrenal and thyroid glands). We also observed a significant decrease in serum estradiol and thyroxine concentrations in methyl-, ethyl-, propyl-, isopropyl-, and isobutylparaben-treated groups. A receptor-binding assay indicated that the relative binding affinities of parabens to estrogen receptors occurred in the order: isobutylparaben>butylparaben>isopropylparaben=propylparaben>ethylparaben. These values were much lower than the binding affinity for 17beta-estradiol. Taken together, long-term exposure to parabens, which show less estrogenic activity than estradiol, can produce suppressive effects on hormonal responsiveness and can disrupt the morphology of reproductive target tissues. In addition, the relation between thyroid weight and thyroid hormone may influence circulating levels of parabens, suggesting the effects of parabens as thyrotoxic during this critical stage of development in female rats.
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