Cardiac proteomics reveals sex chromosome-dependent differences between males and females that arise prior to gonad formation.

TitleCardiac proteomics reveals sex chromosome-dependent differences between males and females that arise prior to gonad formation.
Publication TypeJournal Article
Year of Publication2021
AuthorsShi, W, Sheng, X, Dorr, KM, Hutton, JE, Emerson, JI, Davies, HA, Andrade, TD, Wasson, LK, Greco, TM, Hashimoto, Y, Federspiel, JD, Robbe, ZL, Chen, X, Arnold, AP, Cristea, IM, Conlon, FL
JournalDev Cell
Volume56
Issue21
Pagination3019-3034.e7
Date Published2021 11 08
ISSN1878-1551
KeywordsAnimals, Female, Genes, X-Linked, Gonads, Male, Mice, Proteomics, Sex Characteristics, Sex Chromosomes
Abstract

<p>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.</p>

DOI10.1016/j.devcel.2021.09.022
Alternate JournalDev Cell
PubMed ID34655525
Grant ListR01 HD089275 / HD / NICHD NIH HHS / United States
R01 HL127640 / HL / NHLBI NIH HHS / United States
R01 HL156424 / HL / NHLBI NIH HHS / United States