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Sexual Dimorphism of the Heart: Genetics, Epigenetics, and Development

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 a...

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Autores principales: Deegan, Daniel F., Nigam, Priya, Engel, Nora
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189176/
https://www.ncbi.nlm.nih.gov/pubmed/34124200
http://dx.doi.org/10.3389/fcvm.2021.668252
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author Deegan, Daniel F.
Nigam, Priya
Engel, Nora
author_facet Deegan, Daniel F.
Nigam, Priya
Engel, Nora
author_sort Deegan, Daniel F.
collection PubMed
description 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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spelling pubmed-81891762021-06-10 Sexual Dimorphism of the Heart: Genetics, Epigenetics, and Development Deegan, Daniel F. Nigam, Priya Engel, Nora Front Cardiovasc Med Cardiovascular Medicine 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. Frontiers Media S.A. 2021-05-26 /pmc/articles/PMC8189176/ /pubmed/34124200 http://dx.doi.org/10.3389/fcvm.2021.668252 Text en Copyright © 2021 Deegan, Nigam and Engel. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cardiovascular Medicine
Deegan, Daniel F.
Nigam, Priya
Engel, Nora
Sexual Dimorphism of the Heart: Genetics, Epigenetics, and Development
title Sexual Dimorphism of the Heart: Genetics, Epigenetics, and Development
title_full Sexual Dimorphism of the Heart: Genetics, Epigenetics, and Development
title_fullStr Sexual Dimorphism of the Heart: Genetics, Epigenetics, and Development
title_full_unstemmed Sexual Dimorphism of the Heart: Genetics, Epigenetics, and Development
title_short Sexual Dimorphism of the Heart: Genetics, Epigenetics, and Development
title_sort sexual dimorphism of the heart: genetics, epigenetics, and development
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189176/
https://www.ncbi.nlm.nih.gov/pubmed/34124200
http://dx.doi.org/10.3389/fcvm.2021.668252
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