Cardiac proteomics reveals sex chromosome-dependent differences between males and females that arise prior to gonad formation.
Dev Cell
; 56(21): 3019-3034.e7, 2021 11 08.
Article
em En
| MEDLINE
| ID: mdl-34655525
ABSTRACT
Sex disparities in cardiac homeostasis and heart disease are well documented, with differences attributed to actions of sex hormones. However, studies have indicated sex chromosomes act outside of the gonads to function without mediation by gonadal hormones. Here, we performed transcriptional and proteomics profiling to define differences between male and female mouse hearts. We demonstrate, contrary to current dogma, cardiac sex disparities are controlled not only by sex hormones but also through a sex-chromosome mechanism. Using Turner syndrome (XO) and Klinefelter (XXY) models, we find the sex-chromosome pathway is established by X-linked gene dosage. We demonstrate cardiac sex disparities occur at the earliest stages of heart formation, a period before gonad formation. Using these datasets, we identify and define a role for alpha-1B-glycoprotein (A1BG), showing loss of A1BG leads to cardiac defects in females, but not males. These studies provide resources for studying sex-biased cardiac disease states.
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Base de dados:
MEDLINE
Assunto principal:
Cromossomos Sexuais
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Caracteres Sexuais
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Proteômica
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Gônadas
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article