%0 Journal Article %T Gene expression profile of androgen modulated genes in the murine fetal developing lung. %+ Laboratory of Ontogeny and Reproduction %+ Centre de Recherche en Biologie de la Reproduction (CRBR) %+ Neuroendocrinologie cellulaire et moléculaire %+ Institut Fédératif de Recherches Multidisciplinaires sur les Peptides (IFRMP 23) %+ Department of Obstetrics and Gynaecology %+ Department of Pediatrics %A Bresson, Eva %A Seaborn, Tommy %A Côté, Mélissa %A Cormier, Geneviève %A Provost, Pierre %A Piedboeuf, Bruno %A Tremblay, Yves %Z This work was supported by grants to YT from the Canadian Institutes of Health Research (CIHR) and the Natural Sciences and Engineering Research Council of Canada (NSERC). TS was supported by The Wyeth Pharmaceuticals & CIHR/Rx&D Research Fellowship Program and EB was supported by the Strategic Training Initiative in Research in Reproductive Health Sciences (STIRRHS). %< avec comité de lecture %@ 1477-7827 %J Reproductive Biology and Endocrinology %I BioMed Central %V 8 %N 1 %P 2 %8 2010 %D 2010 %R 10.1186/1477-7827-8-2 %M 20064212 %Z Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetricsJournal articles %X 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. %G English %2 https://inserm.hal.science/inserm-00663543/document %2 https://inserm.hal.science/inserm-00663543/file/1477-7827-8-2.pdf %L inserm-00663543 %U https://inserm.hal.science/inserm-00663543 %~ INSERM %~ CNRS %~ COMUE-NORMANDIE %~ UNIROUEN %~ UNILEHAVRE