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Bisphenol A Exposure at Puberty Disrupts Expression of the Oestrogen Receptor-Alpha in the Hypothalamus of Male and Female Mice

Shantakumari Rajan1,2 , Srikumar Chakravarthi3, Nagaraja Haleagrahara4, Abubakar Abdul Majeed5, Ammu K Radhakrishnan1*

Bisphenol A is a xenoestrogen that interacts with both of the oestrogen receptors, oestrogen receptor alpha (ERα) and oestrogen receptor beta (ERβ). At environmentally low doses, bisphenol A has been reported to influence behaviour and affect development of the brain and reproductive tissues in rodents. In the present study mice were treated daily with a low (50 µg/kg) oral dose of bisphenol A starting on postnatal day (PND) 32 until sacrifice (PND50 or PND100), and at autopsy brain, testis, and uterus of all animals were harvested for analysis. Immunohistochemistry was used to evaluate the changes in the number of cells expressing ERα in the arcuate nucleus and ventromedial nucleus of the hypothalamus. Histological evaluations were performed on the testis and uterus, while analysis of estradiol and testosterone was carried out on mouse serum. At PND50, bisphenol A exposure increased ER expressing neurons in the arcuate nucleus and ventromedial nucleus of the hypothalamus of both male and female mice (p<0.05), while at PND100, bisphenol A exposure only increased ER expressing neurons in the ventromedial nucleus of the hypothalamus of female mice (p<0.05). No adverse effects were observed in the testis of exposed males, except for consistent thickening of the basement membrane. In the females, mild simple hyperplasia of the endometrial glands was observed with no differences between BPA50 and BPA100 groups. Male mice had decreased testosterone and elevated estradiol serum concentrations at PND50 while females were observed to have increased serum estradiol at PND100. Our results show that bisphenol A can modulate oestrogen receptors in the hypothalamus and indicate a comparable effect of exposure in male and female mice during adolescence but a differential effect during adulthood.