Exposure to an environmentally relevant concentration of 17α-ethinylestradiol disrupts craniofacial development of juvenile zebrafish

Abstract

Endocrine disrupting chemicals (EDCs) can interact with native hormone receptors to interfere with and disrupt hormone signalling that is necessary for a broad range of developmental pathways. EDCs are pervasive in our environment, in particular in our waterways, making aquatic wildlife especially vulnerable to their effects. Many of these EDCs are able to bind to and activate oestrogen receptors, causing aberrant oestrogen signalling. Craniofacial development is an oestrogen-sensitive process, with oestrogen receptors expressed in chondrocytes during critical periods of development. Previous studies have demonstrated a negative effect of high concentrations of oestrogen on early craniofacial patterning in the aquatic model organism, the zebrafish (Danio rerio). In order to determine the impacts of exposure to an oestrogenic EDC, we exposed zebrafish larvae and juveniles to either a high concentration to replicate previous studies, or a low, environmentally relevant concentration of the oestrogenic contaminant, 17α-ethinylestradiol. The prolonged / chronic exposure regimen was used to replicate that seen by many animals in natural waterways. We observed changes to craniofacial morphology in all treatments, and most strikingly in the larvae-juveniles exposed to a low concentration of EE2. In the present study, we have demonstrated that the developmental stage at which exposure occurs can greatly impact phenotypic outcomes, and these results allow us to understand the widespread impact of oestrogenic endocrine disruptors. Given the conservation of key craniofacial development pathways across vertebrates, our model can further be applied in defining the risks of EDCs on mammalian organisms.

Keywords

• Endocrine disruptors
• Craniofacial abnormalities
• Oestrogen exposure
• Zebrafish