519
important for repolarization of ventricular cells (Sørhus et al. 2017). Only diminished expression of kcnh2 correlated with the cardiac phenotype in haddock.
Subsequent studies by Diamante et al. (2017) indicated that the kcnh2 regulating
microRNA (miRNA) 133a was induced in mahi-mahi embryos exposed to oil, indicating dysregulation of miRNA may play a role in the downregulation of kcnh2.
These data are consistent with evidence that disruption of Ca
2+
and K
+
fluxes contribute to observed cardiotoxicity by disrupting excitation-contraction coupling in
cardiomyocytes of bluefin tuna (Brette et al. 2014). Overexpression of other cardiac
genes associated with severe heart defects (bmp10, nkx25, and tbx3) was also
observed (Edmunds et al. 2015). Gene ontology categories for perturbations in cardiac function were altered at nearly all time points in mahi-mahi, red drum, and
haddock (Xu et al. 2016a, 2017; Sørhus et al. 2017). Together, these studies have
made it apparent that impaired cardiac function resulting from oil exposure is
related to gene expression changes of both AHR- and non-AHR-mediated
pathways.
Transcriptional changes not connected to AHR pathway genes may also underlie
other oil-related morphological abnormalities, such as reduced eye area and craniofacial/jaw malformations. These abnormalities previously had been attributed to
secondary effects of reduced circulation; however, some may be directly altered
irrespective of cardiac changes (Incardona 2017). In haddock, expression of 12
genes with roles in craniofacial development were significantly altered, which corresponds to reduced eye area and underdevelopment of the jaw (Sørhus et al. 2017).
In mahi-mahi, 35 of the 70 genes associated with visual perception were differentially expressed in 96 hpf exposed larvae (Xu et al. 2016a), and reductions in eye
size and visual acuity were observed (Xu et al. 2018). Similar abnormalities in eye
development following oil exposure were seen in red drum larvae (Magnuson et al.
2018; Xu et al. 2019). The resulting deficiencies in vision or the ability to feed
would have direct impacts on survival in the wild. Other abnormalities that might
affect survival include increased yolk size, corresponding to altered cholesterol
biosynthesis (Xu et al. 2016a; Sørhus et al. 2017), which may reduce yolk absorption and result in underdeveloped embryos that are more susceptible to predation
during the larval phase. Additionally, impaired cholesterol biosynthesis may also
alter membrane structure and contribute to cardiac toxicity. Other predicted organ
level effects of oil based on transcriptomic analyses were focused on nervous system degeneration (Xu et al. 2016a, 2017; Sørhus et al. 2017). Changes in expression of genes involved in nervous system development and functioning were
identified, and brain size was significantly reduced in red drum larvae exposed to
oil (Xu et al. 2017).
Overall, transcriptomic studies following exposure to oil have been instrumental in assessing the basic biological mechanisms of oil toxicity on species in the
Gulf of Mexico. These studies have confirmed previously known pathways of toxicity but also shed light on novel mechanisms. Upregulation of AHR and its downstream stress response gene products is a common biological response across
many fish species. In particular, cyp1a1 and ugt were consistently upregulated,
30 Genetics and Oil: Transcriptomics, Epigenetics, and Population Genomics as Tools…
important for repolarization of ventricular cells (Sørhus et al. 2017). Only diminished expression of kcnh2 correlated with the cardiac phenotype in haddock.
Subsequent studies by Diamante et al. (2017) indicated that the kcnh2 regulating
microRNA (miRNA) 133a was induced in mahi-mahi embryos exposed to oil, indicating dysregulation of miRNA may play a role in the downregulation of kcnh2.
These data are consistent with evidence that disruption of Ca
2+
and K
+
fluxes contribute to observed cardiotoxicity by disrupting excitation-contraction coupling in
cardiomyocytes of bluefin tuna (Brette et al. 2014). Overexpression of other cardiac
genes associated with severe heart defects (bmp10, nkx25, and tbx3) was also
observed (Edmunds et al. 2015). Gene ontology categories for perturbations in cardiac function were altered at nearly all time points in mahi-mahi, red drum, and
haddock (Xu et al. 2016a, 2017; Sørhus et al. 2017). Together, these studies have
made it apparent that impaired cardiac function resulting from oil exposure is
related to gene expression changes of both AHR- and non-AHR-mediated
pathways.
Transcriptional changes not connected to AHR pathway genes may also underlie
other oil-related morphological abnormalities, such as reduced eye area and craniofacial/jaw malformations. These abnormalities previously had been attributed to
secondary effects of reduced circulation; however, some may be directly altered
irrespective of cardiac changes (Incardona 2017). In haddock, expression of 12
genes with roles in craniofacial development were significantly altered, which corresponds to reduced eye area and underdevelopment of the jaw (Sørhus et al. 2017).
In mahi-mahi, 35 of the 70 genes associated with visual perception were differentially expressed in 96 hpf exposed larvae (Xu et al. 2016a), and reductions in eye
size and visual acuity were observed (Xu et al. 2018). Similar abnormalities in eye
development following oil exposure were seen in red drum larvae (Magnuson et al.
2018; Xu et al. 2019). The resulting deficiencies in vision or the ability to feed
would have direct impacts on survival in the wild. Other abnormalities that might
affect survival include increased yolk size, corresponding to altered cholesterol
biosynthesis (Xu et al. 2016a; Sørhus et al. 2017), which may reduce yolk absorption and result in underdeveloped embryos that are more susceptible to predation
during the larval phase. Additionally, impaired cholesterol biosynthesis may also
alter membrane structure and contribute to cardiac toxicity. Other predicted organ
level effects of oil based on transcriptomic analyses were focused on nervous system degeneration (Xu et al. 2016a, 2017; Sørhus et al. 2017). Changes in expression of genes involved in nervous system development and functioning were
identified, and brain size was significantly reduced in red drum larvae exposed to
oil (Xu et al. 2017).
Overall, transcriptomic studies following exposure to oil have been instrumental in assessing the basic biological mechanisms of oil toxicity on species in the
Gulf of Mexico. These studies have confirmed previously known pathways of toxicity but also shed light on novel mechanisms. Upregulation of AHR and its downstream stress response gene products is a common biological response across
many fish species. In particular, cyp1a1 and ugt were consistently upregulated,
30 Genetics and Oil: Transcriptomics, Epigenetics, and Population Genomics as Tools…