Limited sex-biased neural gene expression patterns across strains in Zebrafish (Danio rerio)

Background: Male and female vertebrates typically differ in a range of characteristics, from morphology to physiology to behavior, which are influenced by factors such as the social environment and the internal hormonal and genetic milieu. However, sex differences in gene expression profiles in the brains of vertebrates are only beginning to be understood. Fishes provide a unique complement to studies of sex differences in mammals and birds given that fish show extreme plasticity and lability of sexually dimorphic characters and behaviors during development and even adulthood. Hence, teleost models can give additional insight into sexual differentiation. The goal of this study is to identify neurotranscriptomic mechanisms for sex differences in the brain. Results: In this study we examined whole-brain sex-biased gene expression through RNA-sequencing across four strains of zebrafish. We subsequently conducted systems level analyses by examining gene network dynamics between the sexes using weighted gene coexpression network analysis. Surprisingly, only 61 genes (approximately 0.4% of genes analyzed) showed a significant sex effect across all four strains, and 48 of these differences were male-biased. Several of these genes are associated with steroid hormone biosynthesis. Despite sex differences in a display of stress-related behaviors, basal transcript levels did not predict the intensity of the behavioral display. WGCNA revealed only one module that was significantly associated with sex. Intriguingly, comparing intermodule dynamics between the sexes revealed only moderate preservation. Further we identify sex-specific gene modules. Conclusions: Despite differences in morphology, physiology, and behavior, there is limited sex-biased neural gene expression in zebrafish. Further, genes found to be sex-biased are associated with hormone biosynthesis, suggesting that sex steroid hormones may be key contributors to sexual behavioral plasticity seen in teleosts. A possible mechanism is through regulating specific brain gene networks.