Potential Estrogenic Effect(s) of Parabens at the Neonatal Stage of an Immature Female Rat Mode.

Abstract

This study was performed to examine the estrogenic effects of parabens on hormonal responsiveness and on the morphology of reproductive tissues during a critical developmental stage of female rats. Two hundred immature female Sprague-Dawley rats (n = 10/group) were orally treated with methyl-, ethyl-, propyl-, isopropyl-, butyl-, and isobutylparaben from postnatal day 21 to 40 in a dose-dependent manner based on our previous study [62.5, 250, and 1000 mg/kg of body weight (BW) per day]. A high dose of methyl- and isopropyl paraben (1000 mg/kg of BW per 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 (i.e., decresed in ovaries, kidneys and increased in adrenal glands, thyroid glands, liver) conversely, body weight was not altered following paraben treatment. In all groups exposed to paraben treatment, histological analysis of the ovaries from the immature rats revealed interstitial cell disorders, decreased corpora lutea, an increase in the number of cystic follicles, and thinning of the follicular epithelium, which occurred in a dose-dependent manner. In addition, morphological study of the uterus revealed the myometrial dysplasia such as myometrial hyperplasia in the highest dose of propyl- and isopropyl paraben and in all dose of butyl- and isobutyl parabens. We also observed a significant decrease in serum estradiol and T4 concentrations in methyl-, ethyl-, propyl-, isopropyl-, and isobutylparaben-treated groups (P < 0.01 and 0.05). Taken together, long-term exposure to parabens can produce suppressive effects on hormonal responsiveness and can disrupt the morphology of reproductive target tissues during this critical stage of development in immature female rats. (poster)