Abstract
Important set of studies have demonstrated the endocrine disrupting activity of Bisphenol A (BPA). The present work aimed at defining estrogenic-like activity of several BPA structural analogs, including BPS, BPF, BPAF, and BPAP, on 4- or 7-day post-fertilization (dpf) zebrafish larva as an in vivo model. We measured the induction level of the estrogen-sensitive marker cyp19a1b gene (Aromatase B), expressed in the brain, using three different in situ/in vivo strategies: (1) Quantification of cyp19a1b transcripts using RT-qPCR in wild type 7-dpf larva brains exposed to bisphenols; (2) Detection and distribution of cyp19a1b transcripts using in situ hybridization on 7-dpf brain sections (hypothalamus); and (3) Quantification of the cyp19a1b promoter activity in live cyp19a1b-GFP transgenic zebrafish (EASZY assay) at 4-dpf larval stage. These three different experimental approaches demonstrated that BPS, BPF, or BPAF exposure, similarly to BPA, significantly activates the expression of the estrogenic marker in the brain of developing zebrafish. In vitro experiments using both reporter gene assay in a glial cell context and competitive ligand binding assays strongly suggested that up-regulation of cyp19a1b is largely mediated by the zebrafish estrogen nuclear receptor alpha (zfERα). Importantly, and in contrast to other tested bisphenol A analogs, the bisphenol AP (BPAP) did not show estrogenic activity in our model.
Highlights
Estrogens play important roles in many developmental and physiological processes (Boon et al, 2010) and references therein, including for brain development (Hojo et al, 2008; Hill and Boon, 2009; Bondesson et al, 2014; Coumailleau et al, 2015)
We tested the estrogenic potentials of various bisphenols (BPA, BPS, BPAF, BPF, and bisphenol AP (BPAP)) using the estrogen sensitive biomarker cyp19a1b gene in zebrafish brain
The present work investigated the effects of several bisphenol A analogs on cyp19a1b gene regulation, coding for aromatase B, a well-known target of estrogen signaling pathways in the fish brain
Summary
Estrogens play important roles in many developmental and physiological processes (Boon et al, 2010) and references therein, including for brain development (Hojo et al, 2008; Hill and Boon, 2009; Bondesson et al, 2014; Coumailleau et al, 2015). BPA exposure is linked to numerous adverse health concerns including development, diabetes, obesity, cardiovascular, reproductive disorders, behavioral troubles, chronic respiratory and kidney diseases, and carcinogenesis, likely linked to the endocrine disrupting effects (Vandenberg et al, 2012; Rochester, 2013; Rezg et al, 2014). Owing those potential health concerns, Canada (2009), USA (2010), and the European Union (2011) prohibited the use of BPA in the manufacture of polycarbonate feeding bootles for infants. In France, since January 2015, BPA is forbidden in any food or beverage packaging
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