Sex programs functional protein level dimorphism in the zebrafish gastrointestinal tract

The biochemical composition and functions of non-sexual organs in male and female must be adjusted to support the distinct reproductive purposes of their sexual organs. The gastrointestinal (GI) tract is the primary site for the digestion and absorption of nutrients, as well as the metabolism of orally administered drugs. We utilized an in-depth proteomics approach to determine the molecular basis of sex-based differences in the zebrafish GI tract. Results indicated higher potential of female zebrafish for digestion and absorption of dietary nutrients by lower levels of proteins involved in GI motility, and increased levels of digestive enzymes and reduced levels of intestinal epithelial barrier proteins. While several proteins involved in metabolism of carbohydrates were found at higher levels in males, multiple protein and lipid metabolism proteins were higher in females. Furthermore, the GI tract of males contained lower levels of immune-related proteins and higher levels of anti-aging proteins. Several proteins responsible for drug metabolism, antioxidation and detoxification of xenobiotics showed significantly different quantities between GI tract of male and female zebrafish, suggesting unequal abilities of the two sexes to process these substances. The results of the present study provide molecular knowledge that can aid development of sex-based diet formulation, drug design and therapeutic approaches for the GI tract in future studies. Data are available via ProteomeXchange with identifier PXD054273. • Sexual dimorphism in the zebrafish GI tract was examined using proteomics. • The GI tract of female fish contained higher levels of proteins involved in digestion and absorption. • Sex-based differences were also seen in proteins within drug metabolism, antioxidation and detoxification. • The discoveries can help the development of sex-tailored diet formulation and drug design in aquaculture.