Mouse model of conditional inactivation of androgen receptor : strengths and limits to assess the vulnerability of the neural circuitry underlying male sexual behavior to chronic exposure to Bisphenol A

Abstract : There are human reproduction concerns associated with extensive use of bisphenol A (BPA)-containing plastic and, in particular, the leaching of BPA into food and beverages. In this context, it remains unclear whether and how exposure to BPA interferes with the developmental organization and adult activation of male sexual behavior by testosterone. Rodents have been used from decades to study processes underlying reproductive behaviors and sexual dimorphism. Given the possibility of generating transgenic mouse lines carrying ubiquitous or restricted mutations of specific genes, mouse models provide particularly relevant tools to study the effect of BPA on mouse sexual behavior. In order to assess the effect of chronic exposure to oral BPA at reference doses (no-observed-adverse-effectlevel and tolerable daily intake-TDI) on this behavior, we developed mouse models of developmental or adult exposure to BPA. Until now, BPA has mainly been shown to exert estrogenic activity in vivo but anti-androgenic action could also be involved. As ubiquitous androgen receptor (AR) mutation leads to significant peripheral disruptions preventing mice from expressing proper sexual behavior, we tested the potential mechanisms underlying BPA effects by combining our exposure models to a model of neural conditional inactivation of AR. Only adult exposure to BPA at TDI dose reduced sexual motivation and performance. This deficiency was not restored by sexual experience and was associated with unchanged circulating levels of testosterone. Disrupting the neural AR resulted in behavioral and neuroanatomical effects similar to those induced by adult exposure to TDI dose. Moreover, adult exposure of mutant males to BPA at TDI dose did not trigger additional alteration of sexual behavior, suggesting that BPA and AR mutation share a common mechanism of action. This shows that the neural circuitry underlying male sexual behavior is vulnerable to chronic adult exposure to low dose of BPA. Although we cannot exclude BPA exerts action via other pathways, our results suggest that BPA act in vivo as an anti-androgenic compound.
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Conference papers
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Submitted on : Thursday, August 2, 2018 - 1:17:58 PM
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  • HAL Id : ineris-01852878, version 1

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Marie Picot, Lydie Naule, Clarisse Marie-Luce, Mariangela Martini, Kalina Raskin, et al.. Mouse model of conditional inactivation of androgen receptor : strengths and limits to assess the vulnerability of the neural circuitry underlying male sexual behavior to chronic exposure to Bisphenol A. 27. Conference of European Comparative Endocrinologists (CECE 2014), Aug 2014, Rennes, France. ⟨ineris-01852878⟩

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