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DEVELOPMENTAL BIOLOGY

Sex-chromosome mechanisms contribute to cardiac sex disparities

Nature Reviews Cardiology volume 19, page 5 (2022)Cite this article

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First, transcriptomic and proteomic profiling showed that cardiac sex-specific differences are established by post-transcriptional mechanisms. Next, the researchers used the Four Core Genotype mouse model, in which the actions of gonadal hormones are uncoupled from the effects of sex-chromosome genes, and demonstrated that sex-chromosome mechanisms contribute to cardiac sex-specific disparities. Analyses using the Turner syndrome (XO) and Klinefelter (XXY) mouse models showed that X-linked genes act outside the gonads in a dosage-dependent way to regulate male–female differences in cardiac protein expression. Further assays showed that cardiac sex-specific disparities appear before gonad development. Mouse cardiomyocytes showed sex-biased protein expression as early as embryonic day 9.5 — before gonadal expression of the testis-determining gene Sry and preceding gonad formation. Finally, the investigators assessed the utility of the generated datasets for identifying proteins involved in cardiac disease. They identified α1B-glycoprotein, a protein enriched in embryonic and adult female hearts, and showed that A1bg loss leads to cardiac defects in female but not male mice.

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  1. Nature Reviews Cardiology http://www.nature.com/nrcardio/

    Irene Fernández-Ruiz

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  1. Irene Fernández-Ruiz
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Correspondence to Irene Fernández-Ruiz.

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Fernández-Ruiz, I. Sex-chromosome mechanisms contribute to cardiac sex disparities. Nat Rev Cardiol 19, 5 (2022). https://doi.org/10.1038/s41569-021-00642-0

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  • DOI: https://doi.org/10.1038/s41569-021-00642-0

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