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

Dev Cell. 2021 Oct 12:S1534-5807(21)00766-8. doi: 10.1016/j.devcel.2021.09.022. Online ahead of print.ABSTRACTSex 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.PMID:34655525 | DOI:10.1016/j.devcel.2021.09.022

Source: Developmental Cell - October 16, 2021 Category: Cytology Authors: Wei Shi Xinlei Sheng Kerry M Dorr Josiah E Hutton James I Emerson Haley A Davies Tia D Andrade Lauren K Wasson Todd M Greco Yutaka Hashimoto Joel D Federspiel Zachary L Robbe Xuqi Chen Arthur P Arnold Ileana M Cristea Frank L Conlon Source Type: research