131 EFFECT OF PARABENS ON THE DISRUPTION OF OVARIAN FOLLICLE MATURATION IN A NEONATAL FEMALE RAT MODEL

Abstract

Parabens are widely used as an antimicrobial agent in the preparation of cosmetic consumer products and pharmaceuticals. Parabens are esters of para-hydroxybenzoic acid typically including methyl-, ethyl-, butyl-, isobutyl- and isopropyl-paraben. Recently, parabens have been shown to act as xenoestrogens, a class of endocrine disruptors. In this study, we hypothesised that parabens might disrupt ovarian follicle maturation in female Sprague-Dawley rats during the neonatal period. A total of 55 female rats were divided into 11 groups, each composed of 5 rats. The pups were given daily subcutaneous injections of methyl-, propyl- or butyl-paraben at increasing concentrations of 62.5, 250, or 1000 mg kg^–1 per day on neonatal Day 1 to 7. 17α-Ethinylestradiol (1 mg kg^–1 per day) was used as a positive control. We examined the expression of anti-Müllerian hormone (AMH), which inhibits early folliculogenesis in the ovaries. Levels of AMH mRNA and protein were determined using real-time PCR and Western blot analysis, respectively. We found that the levels of AMH mRNA and protein were dose-dependently increased by methyl- and propyl-paraben compared with the vehicle. In particular, AMH mRNA and protein levels were markedly increased by parabens (methyl- and propyl-) at 1000 mg kg^–1 per day. Data were analysed using a nonparametric one-way ANOVA followed by Dunnett's test for multiple comparisons. The ovaries were excised at postnatal Day 8 and fixed and stained with haematoxylin and eosin for histological analysis. The number of follicles were counted and classified into primordial, primary, or secondary stages via the largest serial sections at the centre of the ovary. Results showed that the total number of follicles and number of primordial follicles were increased by methyl- and propyl-parabens compared with the vehicle. Taken together, these results indicated that methyl- and propyl-parabens may have an estrogenic effect that disrupts the ovarian follicle development necessary for reproductive functions in a neonatal female rat model.