title: Expression profile of androgen-modulated microRNAs in the fetal murine lung.
abstract: BACKGROUND
  Androgens are known to delay lung development. As a consequence, the incidence and morbidity of respiratory distress syndrome of the neonate are higher for male than for female premature infants. We previously reported that many genes were expressed with a sex difference in the mouse developing lung and that several genes were under the control of androgens in the male fetal lung. microRNAs are small non-coding RNAs known to negatively regulate the expression of specific genes. In this study, we examined whether murine miRNAs are under the control of androgens in the male developing lung.
  
  
  METHODS
  Expression profiling of microRNAs was performed by microarrays using RNA extracted from male fetal lungs isolated on gestational day (GD) 17.0 and GD 18.0 after daily injection of pregnant mice from GD 10.0 with the antiandrogen flutamide or vehicle only. To identify putative miRNA target genes, the data obtained here were combined with gene profiling data reported previously using the same RNA preparations. qPCR was used to confirm microarray data with fetal lungs from other litters than those used in microarrays.
  
  
  RESULTS
  Flutamide induced downregulation and upregulation of several miRNAs on GD 17.0 and GD 18.0. Of the 43 mature miRNAs modulated by flutamide on GD 17.0, 60 % were downregulated, whereas this proportion was only of 34 % for the 35 mature miRNAs modulated on GD 18.0. For 29 and 26 flutamide-responsive miRNAs, we found a corresponding target inversely regulated by androgens on GD 17.0 and 18.0, respectively. The androgen-regulated target genes were involved in several biological processes (lipid metabolism, cell proliferation, and lung development) and molecular functions, mainly transcription factor binding.
  
  
  CONCLUSIONS
  Regulation of male lung development involves several miRNAs that are under androgen modulation in vivo.
authors.affiliation: Reproduction, Mother and Youth Health, Centre de Recherche du CHU de Québec, 2705 Laurier Boulevard, Rm T-3-67, Québec City, Québec Canada ; Centre de Recherche en Biologie de la Reproduction (CRBR), Faculté de Médecine, Université Laval, Québec City, Québec Canada.
authors.forename: Wafae
authors.initials: W
authors.lastname: Bouhaddioui
authors.affiliation: Reproduction, Mother and Youth Health, Centre de Recherche du CHU de Québec, 2705 Laurier Boulevard, Rm T-3-67, Québec City, Québec Canada ; Department of Obstetrics/Gynecology and Reproduction, Faculty of Medicine, Université Laval, Québec City, Québec Canada ; Centre de Recherche en Biologie de la Reproduction (CRBR), Faculté de Médecine, Université Laval, Québec City, Québec Canada.
authors.forename: Pierre R
authors.initials: PR
authors.lastname: Provost
authors.affiliation: Reproduction, Mother and Youth Health, Centre de Recherche du CHU de Québec, 2705 Laurier Boulevard, Rm T-3-67, Québec City, Québec Canada ; Department of Obstetrics/Gynecology and Reproduction, Faculty of Medicine, Université Laval, Québec City, Québec Canada ; Centre de Recherche en Biologie de la Reproduction (CRBR), Faculté de Médecine, Université Laval, Québec City, Québec Canada.
authors.forename: Yves
authors.initials: Y
authors.lastname: Tremblay
keywords: Androgens; Lung development; Preterm birth; Respiratory distress syndrome; Sex differences; Surfactant; microRNA