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.

Changes in the concentrations of four maternal steroids during embryonic development in the threespined stickleback (Gasterosteus aculeatus)

“…G. aculeatus has been used as a model system to study how endocrine disrupting chemicals (EDCs) elicit their effects (Bell, ; Bell, ; Hogan et al, ; Pottinger et al, ). It has recently been hypothesized that some EDCs may elicit their effects by inhibiting the metabolism of maternal steroids such that the observed effects are due to an increased exposure of endogenous steroids that are present in the egg (Clairardin et al, ). By demonstrating that G. aculeatus eggs contain a variety of maternally derived steroids and that levels decline early following fertilization, it suggests that embryos could be disrupted by exposure to various steroids depending on the susceptibility of metabolic pathways to inhibition by EDCs.…”

Environmental Health Factors and Sexually Dimorphic Differences in Behavioral Disruptions

“…EDCs likely exert sex-specific behavioral effects by disrupting normal steroid programming of the brain, which could occur through direct binding of neural steroid receptors [155–157], modulation of steroid hormone synthesis or metabolism [156–158], and/or epigenetic alterations of steroid-dependent genes [159]. These changes likely shape how an individual reacts to challenges faced later in life.…”

Avian yolk androgens are metabolized instead of taken up by the embryo during the first days of incubation

“…Exposure of the vertebrate embryo to maternal hormones can have long-lasting effects on offspring morphology, physiology and behaviour in a wide array of taxa, including fish (Brown et al, 2014;Guiguen et al, 2010;Pri-Tal et al, 2011), reptiles (Clairardin et al, 2013;Radder, 2007), birds (Gil, 2008;Schwabl, 1993;von Engelhardt and Groothuis, 2011) and mammals (Del Giudice, 2012;Drea, 2011;Harris and Seckl, 2011). In egglaying vertebrate species, such as birds, almost the entirety of embryonic development occurs outside the mother's body, facilitating measurement and manipulation of this prenatal hormonal exposure.…”