Offshore Crude Oil Disrupts Retinoid Signaling and Eye Development in Larval Atlantic Haddock

Abstract

The aim of this study was to examine the impact of dispersed crude oil on retinoid metabolism and signaling in developing haddock larvae (Melanogrammus aeglefinus). Retinoids and its active metabolites are involved in the regulation of several developmental processes as cell differentiation, growth and limb patterning. Thus, disruption of retinoid signaling, especially during early developmental stages, may have detrimental effects on the organism. In the present study, crude oil exposure during embryonic development and early larvae development disrupted vitamin A signaling by affecting retinoid levels and genes involved in retinoid metabolism. The disruption of retinoid signaling was also evident when looking at the gene expression pattern at several time-points during and after exposure, demonstrating the complexity and temporal factor of retinoid signaling disruption. Exposure during the embryonic period (pre-hatch) resulted in reduced eye size and increased incidence of abnormal eye morphology. The observed changes in expression of retinoid metabolic genes related to the visual cycle indicates that there is a link between the modulated retinoid levels (alltrans retinoic acid and retinol) and increased incidence of abnormal eye development as a result of crude oil exposure. This is the first study to demonstrate disrupted retinoid signaling in fish following crude oil exposure at environmental relevant levels, giving novel insight in to the mechanism of toxicity.

Untangling mechanisms of crude oil toxicity: linking gene expression, morphology and PAHs at two developmental stages in a cold-water fish

“…Crude oil-induced eye developmental defects are well documented. Both reduced eye size (anapthalmia) and reduced size with abnormalities (microphtalmia) are observed Lie et al, 2019;Magnuson et al, 2018). In the present study, eye size was mainly affected in the early exposure, where we find the most severe developmental and functional abnormalities.…”

“…Consistently, impacts on lipid metabolism pathways have been reported in several RNAseq studies (Sørhus et al, 2017;Xu et al, 2017). Several gene expression studies have started to unravel initiating events and key events of adverse outcome pathways of crude oil (Laurel et al, 2019;Lie et al, 2019;McGruer et al, 2019;Sørhus et al, 2017), but there are still knowledge gaps in understanding the underlying mechanisms of crude oil toxicity.…”

“…Zebrafish with no cardiac function (tnnt morpholinos) mimic the oil-induced reduction in eye size (Incardona et al, 2004), suggesting that anapthalmia is secondary to circulatory defects. However, it is also suggested that abnormal cyp-balance disrupts retinoic acid signaling pathway through disturbance of Cyp26, leading to abnormal eye development (Lie et al, 2019;Yamamoto et al, 2000). Another Cyp enzyme, Cyp1b, is also involved in eye development (regulating ocular fissure closure) through both retinoic aciddependent and -independent pathways (Chambers et al, 2007;Williams et al, 2017).…”

“…A circulation-and time-independent expression of bmp10 suggests a direct effect of crude oil on calcium homeostasis. Several signaling pathways linked to cardiac development and proliferation are impacted by the complexity of crude oil exposure, including calciumregulated pathways (Sørhus et al, 2017;Xu et al, 2017), AhR (Yin et al, 2008) and retinoic acid (Lie et al, 2019)-dependent pathways. Disruption of intracellular calcium levels has been shown to reduce cardiomyocyte proliferation leading to smaller ventricles (Ebert et al, 2005;Rottbauer et al, 2001), suggesting that ventricular proliferation is calcium controlled.…”

“…Beyond these circulatory defects that affect cardiac development (Andres-Delgado and Mercader, 2016), other extra-cardiac abnormalities can be secondary to circulatory defects, including craniofacial and eye development, and osmoregulatory and lipid metabolism deficiencies (Incardona et al, 2004;Incardona and Scholz, 2016;Laurel et al, 2019;Sørhus et al, 2017;Sun et al, 2019) Numerous other pathways/endpoints have also been reported beyond the effects downstream of circulatory defects described above. PAH-related disruption of retinoid signaling interrupts eye development (Lie et al, 2019). Craniofacial development and growth can be disrupted by inappropriate signaling in formation processes like midline signaling (Abramyan, 2019;Delling et al, 2013;Kimmel et al, 2001) or secondary to impact on craniofacial muscle apparatus (Shwartz et al, 2012).…”