title: Altered expression of miRNAs in a dihydrotestosterone-induced rat PCOS model.
abstract: BACKGROUND
  The polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine condition characterized by hyperandrogenism, hyperinsulinemia, insulin resistance and chronic anovulation. Regulation and interaction of a multitude of genes required for follicular development are found to be altered in PCOS. MicroRNAs (miRNAs) mediate posttranscriptional gene regulation by binding to the 3´ untranslated region of mRNAs to either inhibit or enhance translation. However, the extent and regulation of miRNA expression in PCOS is poorly understood and the current study is the first to describe altered expression of miRNAs in PCOS.
  
  
  METHODS
  A chronically androgenized [5α-dihydrotestosterone (DHT)-treated] rat model which recapitulates many of the phenotypes of human PCOS, and miRNA PCR array was used to investigate the expression of 349 miRNAs in DHT treated rat ovaries. The ovarian expression of several selected miRNAs was also analyzed by in situ localization experiment.
  
  
  RESULTS
  DHT-treated rats exhibit increased body weight, disrupted estrus cyclicity, decreased insulin sensitivity and decreased ovarian weight, with the latter phenomenon readily rescued by gonadotropin treatment in vivo. In general, 24% of the 349 miRNAs investigated were found to be differentially expressed between DHT-treated and control rats. Most of the differentially expressed miRNAs were found to be predominantly localized in the theca cells of the follicles. In silico analysis of the potential target genes of dysregulated miRNAs revealed their possible involvement in various pathways in the regulation of ovarian function.
  
  
  CONCLUSIONS
  Our current findings suggest that miRNAs are differentially regulated in hyperandrogenism, a condition possibly involved in the dysregulation of steroid hormone receptors and intra-ovarian factors, and that miRNAs may be involved in the etiology of PCOS.
authors.affiliation: Reproductive Biology Unit and Division of Reproductive Medicine, Department of Obstetrics & Gynecology and Cellular & Molecular Medicine, University of Ottawa; Chronic Disease Program, Ottawa Hospital Research Institute, The Ottawa Hospital (General Campus), Ottawa, ON K1H 8L6, Canada. btsang@ohri.ca.
authors.forename: Md Munir
authors.initials: MM
authors.lastname: Hossain
authors.forename: Mingju
authors.initials: M
authors.lastname: Cao
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Karl
authors.initials: K
authors.lastname: Schellander
authors.forename: Dawit
authors.initials: D
authors.lastname: Tesfaye
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Tsang