Behavioral and hypothalamic transcriptome analyses reveal sex-specific responses to phenanthrene exposure in the...

Environmental concentrations of the polycyclic aromatic hydrocarbon phenanthrene can become elevated with petroleum processing, industrial activities, and urban run-off into waterbodies. However, mechanisms related to its neurotoxicity in fish are not fully described. Here, we exposed adult fathead minnows (FHM) to an average measured concentration of 202 μg phenanthrene/L over a 47-d period. Behaviors of male and female FHM were assessed using a novel aquarium test. Phenanthrene exposed females displayed equilibrium loss, while phenanthrene exposed males spent less time in the aquarium bottom, suggesting phenanthrene reduced anxiety-related behavior. To elucidate putative mechanisms underlying behaviors, we determined the hypothalamic transcriptome profile, a critical integration centre for the regulation of behaviors. There were 1075 hypothalamic transcripts differentially expressed between males and females (sex-specific) while 15 transcripts were phenanthrene-specific. Thus, sex of the animal was more pervasive at influencing the transcriptome compared to phenanthrene and this may partially explain the divergent behavioral responses between sexes. Transcripts altered by phenanthrene included palmitoylated 3 membrane protein, plectin 1,ATP synthase membrane subunit c, and mitochondrial ribosomal protein S11. Gene set enrichment analysis revealed less than 5% of the gene networks perturbed by phenanthrene were shared between males and females, thus phenanthrene altered the hypothalamic transcriptome in a sex-specific manner. Gene networks shared between both sexes and associated with phenanthrene-induced neurotoxicity included processes related to mitochondrial respiratory chain dysfunction, epinephrine/norepinephrine release, and glutamate biosynthesis pathways. Such energy deficits and neurotransmitter disruptions are hypothesized to lead to behavioral deficits in fish. This study provides mechanistic insights into phenanthrene-induced neurotoxicity and how it may relate to changes in fish behaviors.