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The Human Placental Sexome Differs between Trophoblast Epithelium and Villous Vessel Endothelium

Molecular mechanisms underlying sexual dimorphism in mammals, fetal sex influences on intrauterine development, and the sex-biased susceptibility for selected diseases in adulthood are novel areas of current research. As importantly, two decades of multifaceted research has established that suscepti...

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Autores principales: Cvitic, Silvija, Longtine, Mark S., Hackl, Hubert, Wagner, Karin, Nelson, Michael D., Desoye, Gernot, Hiden, Ursula
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3812163/
https://www.ncbi.nlm.nih.gov/pubmed/24205377
http://dx.doi.org/10.1371/journal.pone.0079233
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author Cvitic, Silvija
Longtine, Mark S.
Hackl, Hubert
Wagner, Karin
Nelson, Michael D.
Desoye, Gernot
Hiden, Ursula
author_facet Cvitic, Silvija
Longtine, Mark S.
Hackl, Hubert
Wagner, Karin
Nelson, Michael D.
Desoye, Gernot
Hiden, Ursula
author_sort Cvitic, Silvija
collection PubMed
description Molecular mechanisms underlying sexual dimorphism in mammals, fetal sex influences on intrauterine development, and the sex-biased susceptibility for selected diseases in adulthood are novel areas of current research. As importantly, two decades of multifaceted research has established that susceptibility to many adult disorders originates in utero, commonly secondary to the effects of placental dysfunction. We hypothesized that fetal sex influences gene expression and produces functional differences in human placentas. We thus extended previous studies on sexual dimorphism in mammals, which used RNA isolated from whole tissues, to investigate the effects of sex on four cell-phenotypes within a single key tissue, human placental villi. The cells studied included cytotrophoblasts, syncytiotrophoblast, arterial and venous endothelial cells. The cells were isolated from placentas of male or female fetuses and subjected to microarray analysis. We found that fetal sex differentially affected gene expression in a cell-phenotype dependent manner among all four cell-phenotypes. The markedly enriched pathways in males were identified to be signaling pathways for graft-versus-host disease as well as the immune and inflammatory systems that parallel the reported poorer outcome of male fetuses. Our study is the first to compare global gene expression by microarray analysis in purified, characterized, somatic cells from a single human tissue, i.e. placental villi. Importantly, our findings demonstrate that there are cell-phenotype specific, and tissue-specific, sex-biased responses in the human placenta, suggesting fetal sex should be considered as an independent variable in gene expression analysis of human placental villi.
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spelling pubmed-38121632013-11-07 The Human Placental Sexome Differs between Trophoblast Epithelium and Villous Vessel Endothelium Cvitic, Silvija Longtine, Mark S. Hackl, Hubert Wagner, Karin Nelson, Michael D. Desoye, Gernot Hiden, Ursula PLoS One Research Article Molecular mechanisms underlying sexual dimorphism in mammals, fetal sex influences on intrauterine development, and the sex-biased susceptibility for selected diseases in adulthood are novel areas of current research. As importantly, two decades of multifaceted research has established that susceptibility to many adult disorders originates in utero, commonly secondary to the effects of placental dysfunction. We hypothesized that fetal sex influences gene expression and produces functional differences in human placentas. We thus extended previous studies on sexual dimorphism in mammals, which used RNA isolated from whole tissues, to investigate the effects of sex on four cell-phenotypes within a single key tissue, human placental villi. The cells studied included cytotrophoblasts, syncytiotrophoblast, arterial and venous endothelial cells. The cells were isolated from placentas of male or female fetuses and subjected to microarray analysis. We found that fetal sex differentially affected gene expression in a cell-phenotype dependent manner among all four cell-phenotypes. The markedly enriched pathways in males were identified to be signaling pathways for graft-versus-host disease as well as the immune and inflammatory systems that parallel the reported poorer outcome of male fetuses. Our study is the first to compare global gene expression by microarray analysis in purified, characterized, somatic cells from a single human tissue, i.e. placental villi. Importantly, our findings demonstrate that there are cell-phenotype specific, and tissue-specific, sex-biased responses in the human placenta, suggesting fetal sex should be considered as an independent variable in gene expression analysis of human placental villi. Public Library of Science 2013-10-29 /pmc/articles/PMC3812163/ /pubmed/24205377 http://dx.doi.org/10.1371/journal.pone.0079233 Text en © 2013 Cvitic et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Cvitic, Silvija
Longtine, Mark S.
Hackl, Hubert
Wagner, Karin
Nelson, Michael D.
Desoye, Gernot
Hiden, Ursula
The Human Placental Sexome Differs between Trophoblast Epithelium and Villous Vessel Endothelium
title The Human Placental Sexome Differs between Trophoblast Epithelium and Villous Vessel Endothelium
title_full The Human Placental Sexome Differs between Trophoblast Epithelium and Villous Vessel Endothelium
title_fullStr The Human Placental Sexome Differs between Trophoblast Epithelium and Villous Vessel Endothelium
title_full_unstemmed The Human Placental Sexome Differs between Trophoblast Epithelium and Villous Vessel Endothelium
title_short The Human Placental Sexome Differs between Trophoblast Epithelium and Villous Vessel Endothelium
title_sort human placental sexome differs between trophoblast epithelium and villous vessel endothelium
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3812163/
https://www.ncbi.nlm.nih.gov/pubmed/24205377
http://dx.doi.org/10.1371/journal.pone.0079233
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