Novel adverse outcome pathways revealed by chemical genetics in a developing marine fish

Abstract

Crude oil spills are a worldwide ocean conservation threat. Fish are particularly vulnerable to the oiling of spawning habitats, and crude oil causes severe abnormalities in embryos and larvae. However, the underlying mechanisms for these developmental defects are not well understood. Here, we explore the transcriptional basis for four discrete crude oil injury phenotypes in the early life stages of the commercially important Atlantic haddock (Melanogrammus aeglefinus). These include defects in (1) cardiac form and function, (2) craniofacial development, (3) ionoregulation and fluid balance, and (4) cholesterol synthesis and homeostasis. Our findings suggest a key role for intracellular calcium cycling and excitation-transcription coupling in the dysregulation of heart and jaw morphogenesis. Moreover, the disruption of ionoregulatory pathways sheds new light on buoyancy control in marine fish embryos. Overall, our chemicalgenetic approach identifies initiating events for distinct adverse outcome pathways and novel roles for individual genes in fundamental developmental processes.

Polyaromatic hydrocarbons in pollution: a heart‐breaking matter

“…Crude oil exposure has also been shown to alter Ca 2+ -dependent gene expression during embryonic and early larval development in fishes including signalling pathways such as bone morphogenetic protein 10 (BMP10) and myocardin (Sørhus et al 2017). The initiating event for both EC coupling and excitation-transcription coupling are the same (Fig.…”

“…Even though the impact on EC and excitation-transcription coupling is reversible, downstream effects such as circulatory defects and abnormal gene expression, especially during vulnerable developmental stages, may cause irreversible morphological changes. BMP10's primary function of driving cardiac trabeculation (Grego-bessa et al 2007) was found to be up-regulated (4-fold) upon dysregulation of the Ca 2+ controlled gene myocardin in response to crude oil pollutants (Sørhus et al 2017). Taken together, these alterations to electrophysiology, EC coupling and gene expression in the myocyte could contribute to contractile failure, abnormal contractile rhythm and the abnormal cardiac phenotype seen in vivo following PAH exposure (Incardona et al 2004(Incardona et al , 2005Hicken et al 2011;Mager et al 2014;Incardona & Scholz, 2016;Sørhus et al 2016Sørhus et al , 2017.…”

“…) was found to be up‐regulated (4‐fold) upon dysregulation of the Ca 2+ controlled gene myocardin in response to crude oil pollutants (Sørhus et al . ). Taken together, these alterations to electrophysiology, EC coupling and gene expression in the myocyte could contribute to contractile failure, abnormal contractile rhythm and the abnormal cardiac phenotype seen in vivo following PAH exposure (Incardona et al .…”

Parental stressor exposure simultaneously conveys both adaptive and maladaptive larval phenotypes through epigenetic inheritance in the zebrafish (Danio rerio)

“…Whether acute or chronic, exposure to crude oil and the thousands of compounds it contains can be a potent environmental stressor. In particular, for fish, crude oil exposure may occur via the gills, via diet or by skin contact (Tierney et al, 2013), deeply affecting all developmental stages of fish, from molecular to behavioral levels of organization (Bautista et al, 2019;Brette et al, 2014;Carls et al, 2008;Dubansky et al, 2013;Edmunds et al, 2015;Esbaugh et al, 2016;Frantzen et al, 2012;González-Doncel et al, 2008;Incardona et al, 2004Incardona et al, , 2012Khursighara et al, 2016;Mager et al, 2014;Nelson et al, 2016;Perrichon et al, 2016;Sørhus et al, 2017;Xu et al, 2017a,b). For example, some studies have reported the existence of a link between embryonic exposure to oil and modified phenotypes exhibited during later developmental stages, such as reduced swimming performance and interference with normal heart development (Hicken et al, 2011;Huang et al, 2014;Incardona et al, 2015;Mager et al, 2014).…”

Reproductive Ecology of Dragonfishes (Stomiiformes: Stomiidae) in the Gulf of Mexico

“…The findings most relevant to this study, however, were the heightened levels of PAHs in ovaries of fishes collected between 2015 and 2017, with eggs containing 13× more PAHs than other tissues. Furthermore, PAH levels from the eggs of fishes collected during this period were above levels known to cause abnormalities in developing fishes (Sundberg et al, 2006;Sørhus et al, 2017). An explanation for the differences in PAH concentration between eggs and somatic tissue is the maternal transfer of contaminants to offspring.…”