Sexual Dimorphism of the Heart: Genetics, Epigenetics, and Development.
Sexual Dimorphism of the Heart: Genetics, Epigenetics, and Development.
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DOI：
10.3389/fcvm.2021.668252
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发表时间：
2021
影响因子：
3.6
通讯作者：
Engel N
中科院分区：
文献类型：
--
作者：
Deegan DF;Nigam P;Engel N
基因组技术的民主化揭示了每个成人组织在表达模式上的深刻性别偏见，甚至在心脏等没有明显差异的器官中也是如此。随着人们对男性和女性心脏病理生理学差异的认识日益加深，人们有了令人兴奋的机会来探索心脏性别差异是如何在发育过程中建立起来的。虽然性二型性传统上归因于激素的影响，但在心脏发育早期观察到的表达和表观遗传学性别偏见只能由性染色体组成的差异来解释，即女性的XX和男性的XY。事实上，与X和Y染色体相关的基因，其中许多编码调节因子，在心脏祖细胞和随后的每个发育阶段都有表达。性染色体组成的影响可能解释了为什么许多起源于性腺形成之前的先天性心脏病在表现、死亡率和发病率方面表现出性别偏见。在受精后不久建立的一些转录和表观遗传性偏见在心脏谱系中持续存在，这表明早期表观遗传事件在早期胚胎发生之后持续存在。重要的是，当性荷尔蒙开始循环时，它们会遇到一个在功能上已经不同于性别的心脏基因组。虽然性激素对心脏功能的影响有丰富的知识，但我们认为与性染色体相关的基因及其下游靶点也是造成男性和女性心脏差异的原因。此外，确定荷尔蒙如何影响性染色体效应，无论是对抗性还是协同性，将增强我们对性别差异是如何建立起来的理解。我们还探索了发育中的心脏的性别二型性预测对环境信号的性别特异性反应的可能性，并预示着出生后性别偏见的健康相关结果。
The democratization of genomic technologies has revealed profound sex biases in expression patterns in every adult tissue, even in organs with no conspicuous differences, such as the heart. With the increasing awareness of the disparities in cardiac pathophysiology between males and females, there are exciting opportunities to explore how sex differences in the heart are established developmentally. Although sexual dimorphism is traditionally attributed to hormonal influence, expression and epigenetic sex biases observed in early cardiac development can only be accounted for by the difference in sex chromosome composition, i.e., XX in females and XY in males. In fact, genes linked to the X and Y chromosomes, many of which encode regulatory factors, are expressed in cardiac progenitor cells and at every subsequent developmental stage. The effect of the sex chromosome composition may explain why many congenital heart defects originating before gonad formation exhibit sex biases in presentation, mortality, and morbidity. Some transcriptional and epigenetic sex biases established soon after fertilization persist in cardiac lineages, suggesting that early epigenetic events are perpetuated beyond early embryogenesis. Importantly, when sex hormones begin to circulate, they encounter a cardiac genome that is already functionally distinct between the sexes. Although there is a wealth of knowledge on the effects of sex hormones on cardiac function, we propose that sex chromosome-linked genes and their downstream targets also contribute to the differences between male and female hearts. Moreover, identifying how hormones influence sex chromosome effects, whether antagonistically or synergistically, will enhance our understanding of how sex disparities are established. We also explore the possibility that sexual dimorphism of the developing heart predicts sex-specific responses to environmental signals and foreshadows sex-biased health-related outcomes after birth.
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DOI：
10.1161/atvbaha.116.307301
发表时间：
2017-05
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Arnold AP;Cassis LA;Eghbali M;Reue K;Sandberg K
通讯作者：
Sandberg K
影响因子：
10.9
作者：
Arnold, Arthur P.;van Nas, Atila;Lusis, Aldons J.
通讯作者：
Lusis, Aldons J.
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
7
作者：
Blekhman, Ran;Marioni, John C.;Gilad, Yoav
通讯作者：
Gilad, Yoav
影响因子：
--
作者：
Abramowitz, Lara K;Olivier-Van Stichelen, Stephanie;Hanover, John A
通讯作者：
Hanover, John A