title: MicroRNA Species in Follicular Fluid Associating With Polycystic Ovary Syndrome and Related Intermediary Phenotypes.
abstract: Polycystic ovary syndrome (PCOS) has a largely unknown etiology and presents with a clinical heterogeneous patient group. Small noncoding microRNA (miRNA) might prove promising as biomarker candidates for PCOS patient stratification. Altered miRNA expression profiles have been observed in few studies.
  
  
  
  The aim was to assess the miRNA expression profile in follicular fluid from PCOS patients and healthy, regularly cycling, matched controls.
  
  
  
  Experimental case-control study including 49 PCOS women (19 of which were hyperandrogenic and 30 normo-androgenic) and 21 healthy matched women all undergoing in vitro fertilization treatment.
  
  
  
  Anthropometric and relevant clinical baseline measurements were obtained. Relative expression of miRNA levels were estimated using miRNA quantitative PCR arrays and validated by quantitative RT-PCR. Correlation between miRNAs and clinical relevant measurements was estimated.
  
  
  
  PCOS women, both normo-androgenic and hyperandrogenic, had decreased levels of miR-24-3p, -29a, -151-3p, and -574-3p compared with controls. Furthermore, miR-518f-3p was differentially expressed within the PCOS group with high levels observed in the hyperandrogenic group compared with the normo-androgenic PCOS patients. Serum levels of total and free T were positively correlated with miR-518f-3p in PCOS subjects (P = .001). Distinction between PCOS and controls could be made using miR-151-3p alone with an area under the curve of 0.91 or a combination of four selected miRNAs (area under the curve, 0.93). Bioinformatic target analysis points to an involvement of these miRNAs in biological pathways involving regulation of cell proliferation, extracellular matrix, and processes in intermediary metabolism.
  
  
  
  Our study provides evidence that the miRNA expression profile in follicular fluid is altered in PCOS and indicates that specific follicular fluid miRNAs are associated with phenotypical traits of PCOS. An altered miRNA profile holds potentials for new methods of PCOS patient stratification and may contribute to and in part explain the heterogeneous nature found within PCOS women.
authors.affiliation: Department of Science, Systems and Models (A.E.S., L.T.D.), Roskilde University, Roskilde, Denmark; Fertility Clinic Region Sjaelland (L.W., A.L.M.E.), Holbaek Hospital, Holbaek, Denmark; and The Danish Diabetes Academy (A.E.S.), Odense University Hospital, Odense C, Denmark.
authors.forename: Anja E
authors.initials: AE
authors.lastname: Sørensen
authors.affiliation: Department of Science, Systems and Models (A.E.S., L.T.D.), Roskilde University, Roskilde, Denmark; Fertility Clinic Region Sjaelland (L.W., A.L.M.E.), Holbaek Hospital, Holbaek, Denmark; and The Danish Diabetes Academy (A.E.S.), Odense University Hospital, Odense C, Denmark.
authors.forename: Marie Louise
authors.initials: ML
authors.lastname: Wissing
authors.affiliation: Department of Science, Systems and Models (A.E.S., L.T.D.), Roskilde University, Roskilde, Denmark; Fertility Clinic Region Sjaelland (L.W., A.L.M.E.), Holbaek Hospital, Holbaek, Denmark; and The Danish Diabetes Academy (A.E.S.), Odense University Hospital, Odense C, Denmark.
authors.forename: Anne Lis M
authors.initials: AL
authors.lastname: Englund
authors.affiliation: Department of Science, Systems and Models (A.E.S., L.T.D.), Roskilde University, Roskilde, Denmark; Fertility Clinic Region Sjaelland (L.W., A.L.M.E.), Holbaek Hospital, Holbaek, Denmark; and The Danish Diabetes Academy (A.E.S.), Odense University Hospital, Odense C, Denmark.
authors.forename: Louise T
authors.initials: LT
authors.lastname: Dalgaard
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D015571:Follicular Fluid / Q000378:metabolism*; D006801:Humans; D017588:Hyperandrogenism / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D010641:Phenotype; D011085:Polycystic Ovary Syndrome / Q000235:genetics* / Q000473:pathology*
chemical_list: D035683:MicroRNAs