Understanding the molecular basis of sexual dimorphism in the cardiovascular system may contribute to the improvement of the outcome in biological, pharmacological, and toxicological studies as well as on the development of sex-based drugs and therapeutic approaches. Label-free protein quantification using high-resolution mass spectrometry was applied to detect sex-based proteome differences in the heart of zebrafish Danio rerio. Out of almost 3000 unique identified proteins in the heart, 79 showed significant abundance differences between male and female fish. The functional differences were mapped using enrichment analyses. Our results suggest that a large amount of materials needed for reproduction (e.g., sugars, lipids, proteins, etc.) may impose extra pressure on blood, vessels, and heart on their way toward the ovaries. In the present study, the female's heart shows a clear sexual dimorphism by changing abundance levels of numerous proteins, which could be a way to safely overcome material-induced elevated pressures. These proteins belong to the immune system, oxidative stress response, drug metabolization, detoxification, energy, metabolism, and so on. In conclusion, we showed that sex can induce dimorphism at the molecular level in nonsexual organs such as heart and must be considered as an important factor in cardiovascular research. Data are available via ProteomeXchange with identifier PXD023506.

Department of Immunotechnology Lund University Lund 223 87 Sweden

Faculty of Fisheries and Protection of Waters CENAKVA University of South Bohemia in České Budějovice Vodňany 370 05 České Budějovice Czech Republic

National Bioinformatics Infrastructure Sweden Science for Life Laboratory Lund University Lund 223 87 Sweden

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