Delayed onset of puberty in male offspring from bisphenol A-treated dams is followed by the modulation of gene expression in the hypothalamic–pituitary–testis axis in adulthood
Isabela M. Oliveira A , Renata M. Romano A , Patricia de Campos A , Monica D. Cavallin A , Claudio A. Oliveira B and Marco A. Romano A CA Laboratory of Reproductive Toxicology, Department of Pharmacy, State University of Centro-Oeste, Rua Simeao Camargo Varela de Sa, 03, 85040-080, Parana, Brazil.
B Laboratory of Hormonal Dosages, Department of Animal Reproduction, Faculty of Veterinary Medicine, University of Sao Paulo, Av. Prof. Dr Orlando Marques de Paiva, 87, 05508-270, Sao Paulo, Brazil.
C Corresponding author. Email: maromano17@gmail.com
Reproduction, Fertility and Development 29(12) 2496-2505 https://doi.org/10.1071/RD17107
Submitted: 22 October 2016 Accepted: 28 May 2017 Published: 23 June 2017
Abstract
Bisphenol A (BPA) is a synthetic endocrine-disrupting chemical of high prevalence in the environment, which may affect the function of the hypothalamic–pituitary–testis (HPT) axis in adult rats. The aim of the present study was to evaluate whether exposure to BPA during hypothalamic sexual differentiation at doses below the reproductive no observable adverse effect level of the World Health Organization causes changes in the regulation of the HPT axis. For this, 0.5 or 5 mg kg−1 BPA was injected subcutaneously to the mothers from gestational day 18 to postnatal day (PND) 5. In adulthood (PND90), the mRNA expression of genes related to HPT axis was evaluated in hypothalamus, pituitary and testis. Hypothalamic expression of gonadotrophin-releasing hormone (Gnrh) and estrogen receptor 2 (Esr2) mRNA was increased in both BPA-treated groups compared to control group. In the pituitary, follicle stimulating hormone beta subunit (Fshb) and androgen receptor (Ar) mRNA expression was increased compared to control group in rats treated with 0.5 mg kg−1 of BPA, whereas estrogen receptor 1 (Esr1) mRNA expression was only increased in the group treated with 5 mg kg−1 of BPA, compared to control group. In the testis, there was increased expression of FSH receptor (Fshr) and inhibin beta B subunit (Inhbb) transcripts only in rats treated with 0.5 mg kg−1 of BPA. Serum testosterone and LH concentrations were increased in the group treated with 5 mg kg−1 of BPA. The results of the present study demonstrate for the first time that perinatal exposure to low doses of BPA during the critical period of hypothalamic sexual differentiation modifies the activity of the HPT axis in the offspring, with consequences for later life in adult rats.
Additional keywords: endocrine disrupting chemical, perinatal exposure.
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