title: Panel of five microRNAs as potential biomarkers for the diagnosis and assessment of male infertility.
abstract: OBJECTIVE
  To validate a set of five microRNAs (miRNAs) as specific biomarkers for the assessment of male infertility.
  
  
  METHODS
  Quantitative real-time polymerase chain reaction (qRT-PCR) validation study.
  
  
  METHODS
  University research and clinical institutes.
  
  
  METHODS
  Two hundred twenty-six men presenting at an infertility clinic.
  
  
  METHODS
  None.
  
  
  METHODS
  Validation analysis of a set of miRNAs in human purified spermatozoa and testicular biopsies.
  
  
  RESULTS
  Five miRNAs (hsa-miR-34b*, hsa-miR-34b, hsa-miR-34c-5p, hsa-miR-429, and hsa-miR-122) were confirmed with the use of qRT-PCR analysis in validation sets in patients with different forms of spermatogenic impairments (subfertile and nonobstructive azoospermia [NOA]) and control subjects. We found that hsa-miR-429 was significantly increased and the four other miRNAs were decreased in both tested groups compared with normal control subjects. Computing the area under the receiver operating characteristic curve (AUC) value for each of the five miRNAs, we showed that they separated the tested groups with high accuracy (range 0.777-0.988), except for hsa-miR-429 (AUC 0.475), in patient samples with NOA. Furthermore, with the use of support vector machine classification combining these five miRNAs, we found that they discriminated individuals with, respectively, subfertility and NOA from control subjects with an accuracy of 98.65% and 99.91%, a specificity of 98.44% and 99.69%, and a sensitivity of 98.83% and 100%.
  
  
  CONCLUSIONS
  Our finding suggests that these five miRNAs have potential as novel noninvasive biomarkers to diagnose patients with subfertility. Except for hsa-miR-429, the combination of these miRNAs with other conventional tests would improve the diagnostic accuracy for detecting patients with different forms of NOA.
authors.affiliation: Department of Human Genetics, IVF and Andrology Laboratory, Saarland University, Saar, Germany; Department of Obstetrics and Gynecology, IVF and Andrology Laboratory, Saarland University, Saar, Germany. Electronic address: masood@daad-alumni.de.
authors.forename: Masood
authors.initials: M
authors.lastname: Abu-Halima
authors.affiliation: Department of Obstetrics and Gynecology, IVF and Andrology Laboratory, Saarland University, Saar, Germany.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Hammadeh
authors.affiliation: Department of Human Genetics, IVF and Andrology Laboratory, Saarland University, Saar, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Backes
authors.affiliation: Department of Human Genetics, IVF and Andrology Laboratory, Saarland University, Saar, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Fischer
authors.affiliation: Department of Human Genetics, IVF and Andrology Laboratory, Saarland University, Saar, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Leidinger
authors.affiliation: Faculty of Medicine, Islamic University of Gaza, Gaza Strip, Palestine.
authors.forename: Abdel Monem
authors.initials: AM
authors.lastname: Lubbad
authors.affiliation: Department of Human Genetics, IVF and Andrology Laboratory, Saarland University, Saar, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Keller
authors.affiliation: Department of Human Genetics, IVF and Andrology Laboratory, Saarland University, Saar, Germany.
authors.forename: Eckart
authors.initials: E
authors.lastname: Meese
mesh_terms: D016022:Case-Control Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D007248:Infertility, Male / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D010641:Phenotype; D011237:Predictive Value of Tests; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D013091:Spermatogenesis / Q000235:genetics; D013094:Spermatozoa / Q000737:chemistry; D013737:Testis / Q000737:chemistry
chemical_list: D005819:Genetic Markers; D035683:MicroRNAs
keywords: male infertility; microRNA; nonobstructive azoospermia; seminal plasma; spermatozoa