Abstract
Differential gene expression in two sexes is widespread throughout the animal kingdom, giving rise to sex-dimorphic gene activities and sex-dependent adaptability to environmental cues, diets, growth and development as well as susceptibility to diseases. Here, we present a study using a toxicogenomic approach to investigate metabolic genes that show sex-dimorphic expression in the zebrafish liver triggered by several chemicals. Our analysis revealed that, besides the known genes for xenobiotic metabolism, many functionally diverse metabolic genes, such as ELOVL fatty acid elongase, DNA-directed RNA polymerase, and hydroxysteroid dehydrogenase, were also sex-dimorphic in their response to chemical treatments. Moreover, sex-dimorphic responses were also observed at the pathway level. Pathways belonging to xenobiotic metabolism, lipid metabolism, and nucleotide metabolism were enriched with sex-dimorphically expressed genes. We also observed temporal differences of the sex-dimorphic responses, suggesting that both genes and pathways are differently correlated during different periods of chemical perturbation. The ubiquity of sex-dimorphic activities at different biological hierarchies indicate the importance and the need of considering the sex factor in many areas of biological researches, especially in toxicology and pathology.
Highlights
Sexual dimorphism occurs at various biological levels throughout the life span of the organisms that reproduce sexually, where males and females show obvious anatomical, physiological, and behavioral differences
Annotated genes involve in a wide range of metabolism including xenobiotic metabolism are considered
Genes missing from microarray data under one or more chemical-treatment conditions were eliminated
Summary
Sexual dimorphism occurs at various biological levels throughout the life span of the organisms that reproduce sexually, where males and females show obvious anatomical, physiological, and behavioral differences. Due to the different strategies adopted to maximize survival fitness, exogenous perturbations could trigger observable disparity of endogenous alterations that possibly link to phenotypic variations in opposite sexes This is evident by the increasing reports that males and females differ in susceptibility to diseases, vulnerability to pharmaceuticals in terms of drug efficacy and adverse drug reactions, as well as differential responsiveness to various xenobiotics [1,2,3]. Researchers have observed that a large number of genes exhibited profound sexual differences at the transcriptomic level in nongonadal tissues such as brain and liver [11,12,13,14,15,16,17,18,19] These reports collectively suggest that sexual dimorphism stems from sexdependent genetic and hormonal regulation, and is widespread across many, if not all, organs. The hormonal and transcriptomic differences between opposite sexes are well known under normal physiology, there is still limited information on sexdependent gene expression in responding to exogenous perturbations [20]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
