title: In ovo inhibition of steroid metabolism by bisphenol-A as a potential mechanism of endocrine disruption.
abstract: During embryonic development, endogenous signals, for example steroid hormones, and exogenous signals, for example endocrine disrupting chemicals (EDCs), have the capacity to produce phenotypic effects that persist into adulthood. As the actions of steroids are mediated through the binding of steroid receptors, most studies of EDCs have assumed that they too elicit their effects by binding steroid receptors. We tested an alternative hypothesis, namely that EDCs elicit their effects during embryonic development by disrupting the metabolism of maternally derived steroids, thereby allowing maternally derived steroids to bind steroid receptors and elicit effects. Specifically, we examined the ability of the EDC, bisphenol-A (BPA) to inhibit the normal metabolism of oestradiol during the first nine days of embryonic development in the red-eared slider turtle (Trachemys scripta). We found that, when BPA was present, oestrogen metabolism was inhibited when compared to control eggs. In particular, the formation of oestrone sulfate was blocked in BPA-treated eggs. We postulate that the oestrogenic effects of EDCs may be driven, at least in part, by inappropriate oestrogen signalling. The retention of oestrogens at points of development when they would normally be metabolized to inactive forms might also help explain low-dose effects frequently reported for EDCs.
authors.affiliation: School of Biological Sciences, Illinois State University, Campus Box 4120, Normal, IL 61790-4120, USA.
authors.forename: Sandrine G
authors.initials: SG
authors.lastname: Clairardin
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Paitz
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Bowden
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000633:toxicity*; D002853:Chromatography, Liquid; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D052244:Endocrine Disruptors / Q000008:administration & dosage / Q000633:toxicity*; D004958:Estradiol / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D007087:Illinois; D010063:Ovum / Q000187:drug effects / Q000378:metabolism; D010636:Phenols / Q000008:administration & dosage / Q000633:toxicity*; D011897:Random Allocation; D053719:Tandem Mass Spectrometry; D014426:Turtles / Q000254:growth & development / Q000378:metabolism*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D004958:Estradiol; D004967:Estrogens; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: oestradiol; oestrone sulfate; steroid metabolism