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Gene expression profile of androgen modulated genes in the murine fetal developing lung
BACKGROUND: Accumulating evidences suggest that sex affects lung development. Indeed, a higher incidence of respiratory distress syndrome is observed in male compared to female preterm neonates at comparable developmental stage and experimental studies demonstrated an androgen-related delay in male...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2822783/ https://www.ncbi.nlm.nih.gov/pubmed/20064212 http://dx.doi.org/10.1186/1477-7827-8-2 |
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author | Bresson, Eva Seaborn, Tommy Côté, Mélissa Cormier, Geneviève Provost, Pierre R Piedboeuf, Bruno Tremblay, Yves |
author_facet | Bresson, Eva Seaborn, Tommy Côté, Mélissa Cormier, Geneviève Provost, Pierre R Piedboeuf, Bruno Tremblay, Yves |
author_sort | Bresson, Eva |
collection | PubMed |
description | BACKGROUND: Accumulating evidences suggest that sex affects lung development. Indeed, a higher incidence of respiratory distress syndrome is observed in male compared to female preterm neonates at comparable developmental stage and experimental studies demonstrated an androgen-related delay in male lung maturation. However, the precise mechanisms underlying these deleterious effects of androgens in lung maturation are only partially understood. METHODS: To build up a better understanding of the effect of androgens on lung development, we analyzed by microarrays the expression of genes showing a sexual difference and those modulated by androgens. Lungs of murine fetuses resulting from a timely mating window of 1 hour were studied at gestational day 17 (GD17) and GD18, corresponding to the period of surge of surfactant production. Using injections of the antiandrogen flutamide to pregnant mice, we hunted for genes in fetal lungs which are transcriptionally modulated by androgens. RESULTS: Results revealed that 1844 genes were expressed with a sexual difference at GD17 and 833 at GD18. Many genes were significantly modulated by flutamide: 1597 at GD17 and 1775 at GD18. Datasets were analyzed by using in silico tools for reconstruction of cellular pathways. Between GD17 and GD18, male lungs showed an intensive transcriptional activity of proliferative pathways along with the onset of lung differentiation. Among the genes showing a sex difference or an antiandrogen modulation of their expression, we specifically identified androgen receptor interacting genes, surfactant related genes in particularly those involved in the pathway leading to phospholipid synthesis, and several genes of lung development regulator pathways. Among these latter, some genes related to Shh, FGF, TGF-beta, BMP, and Wnt signaling are modulated by sex and/or antiandrogen treatment. CONCLUSION: Our results show clearly that there is a real delay in lung maturation between male and female in this period, the latter pursuing already lung maturation while the proper is not yet fully engaged in the differentiation processes at GD17. In addition, this study provides a list of genes which are under the control of androgens within the lung at the moment of surge of surfactant production in murine fetal lung. |
format | Text |
id | pubmed-2822783 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-28227832010-02-17 Gene expression profile of androgen modulated genes in the murine fetal developing lung Bresson, Eva Seaborn, Tommy Côté, Mélissa Cormier, Geneviève Provost, Pierre R Piedboeuf, Bruno Tremblay, Yves Reprod Biol Endocrinol Research BACKGROUND: Accumulating evidences suggest that sex affects lung development. Indeed, a higher incidence of respiratory distress syndrome is observed in male compared to female preterm neonates at comparable developmental stage and experimental studies demonstrated an androgen-related delay in male lung maturation. However, the precise mechanisms underlying these deleterious effects of androgens in lung maturation are only partially understood. METHODS: To build up a better understanding of the effect of androgens on lung development, we analyzed by microarrays the expression of genes showing a sexual difference and those modulated by androgens. Lungs of murine fetuses resulting from a timely mating window of 1 hour were studied at gestational day 17 (GD17) and GD18, corresponding to the period of surge of surfactant production. Using injections of the antiandrogen flutamide to pregnant mice, we hunted for genes in fetal lungs which are transcriptionally modulated by androgens. RESULTS: Results revealed that 1844 genes were expressed with a sexual difference at GD17 and 833 at GD18. Many genes were significantly modulated by flutamide: 1597 at GD17 and 1775 at GD18. Datasets were analyzed by using in silico tools for reconstruction of cellular pathways. Between GD17 and GD18, male lungs showed an intensive transcriptional activity of proliferative pathways along with the onset of lung differentiation. Among the genes showing a sex difference or an antiandrogen modulation of their expression, we specifically identified androgen receptor interacting genes, surfactant related genes in particularly those involved in the pathway leading to phospholipid synthesis, and several genes of lung development regulator pathways. Among these latter, some genes related to Shh, FGF, TGF-beta, BMP, and Wnt signaling are modulated by sex and/or antiandrogen treatment. CONCLUSION: Our results show clearly that there is a real delay in lung maturation between male and female in this period, the latter pursuing already lung maturation while the proper is not yet fully engaged in the differentiation processes at GD17. In addition, this study provides a list of genes which are under the control of androgens within the lung at the moment of surge of surfactant production in murine fetal lung. BioMed Central 2010-01-08 /pmc/articles/PMC2822783/ /pubmed/20064212 http://dx.doi.org/10.1186/1477-7827-8-2 Text en Copyright ©2010 Bresson et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Bresson, Eva Seaborn, Tommy Côté, Mélissa Cormier, Geneviève Provost, Pierre R Piedboeuf, Bruno Tremblay, Yves Gene expression profile of androgen modulated genes in the murine fetal developing lung |
title | Gene expression profile of androgen modulated genes in the murine fetal developing lung |
title_full | Gene expression profile of androgen modulated genes in the murine fetal developing lung |
title_fullStr | Gene expression profile of androgen modulated genes in the murine fetal developing lung |
title_full_unstemmed | Gene expression profile of androgen modulated genes in the murine fetal developing lung |
title_short | Gene expression profile of androgen modulated genes in the murine fetal developing lung |
title_sort | gene expression profile of androgen modulated genes in the murine fetal developing lung |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2822783/ https://www.ncbi.nlm.nih.gov/pubmed/20064212 http://dx.doi.org/10.1186/1477-7827-8-2 |
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