title: Levels of the retinoic acid synthesizing enzyme aldehyde dehydrogenase-1A2 are lower in testicular tissue from men with infertility.
abstract: OBJECTIVE
  To determine whether decreased testicular levels of enzymes necessary for retinoic acid biosynthesis were associated with male infertility, as retinoic acid is known to be necessary for spermatogenesis.
  
  
  METHODS
  Observational analysis of testicular tissue samples, sperm indices, and serum hormone concentrations.
  
  
  METHODS
  Two infertility centers in Chile.
  
  
  METHODS
  32 infertile men and 11 control men.
  
  
  METHODS
  Measurement of the three enzymes necessary for retinoic acid biosynthesis, aldehyde dehydrogenase (ALDH) 1A1, 1A2, and 1A3, in testicular tissue by a novel liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) peptide assay.
  
  
  METHODS
  ALDH isozyme levels compared by type of infertility and correlated with testicular germ cell numbers, sperm parameters, and serum and intratesticular hormone concentrations.
  
  
  RESULTS
  Men with infertility had statistically significantly reduced levels of ALDH1A2 but not ALDH1A1 or ALDH1A3 in their testicular tissue compared with men with normal spermatogenesis. The ALDH1A2 protein levels were strongly correlated with the number of germ cells found via testicular biopsy.
  
  
  CONCLUSIONS
  These findings suggest that ALDH1A2 is the enzyme involved in retinoic acid biosynthesis in human germ cells. Further study of the relationship between intratesticular ALDH1A2 and male infertility is warranted to determine whether men with infertility have a reduced ability to synthesize retinoic acid within their germ cells that could impair spermatogenesis.
authors: Department of Medicine, University of Washington, Seattle, Washington. Electronic address: jamory@u.washington.edu.
authors: John K
authors: JK
authors: Amory
authors: Department of Pharmaceutics, University of Washington, Seattle, Washington.
authors: Samuel
authors: S
authors: Arnold
authors: Institute of Maternal and Child Research, School of Medicine, University of Chile, Santiago, Chile.
authors: María C
authors: MC
authors: Lardone
authors: Andrés Bello University, Santiago, Chile.
authors: Antonio
authors: A
authors: Piottante
authors: San Borja Arriarán Clinical Hospital, Santiago, Chile.
authors: Mauricio
authors: M
authors: Ebensperger
authors: Department of Pharmaceutics, University of Washington, Seattle, Washington.
authors: Nina
authors: N
authors: Isoherranen
authors: Department of Urology, University of Washington, Seattle, Washington.
authors: Charles H
authors: CH
authors: Muller
authors: Department of Urology, University of Washington, Seattle, Washington.
authors: Thomas
authors: T
authors: Walsh
authors: Institute of Maternal and Child Research, School of Medicine, University of Chile, Santiago, Chile.
authors: Andrea
authors: A
authors: Castro
mesh_terms: D000328:Adult; D000080924:Aldehyde Dehydrogenase 1 Family; D015415:Biomarkers / Q000378:metabolism; D002677:Chile / Q000453:epidemiology; D006801:Humans; D007248:Infertility, Male / Q000175:diagnosis / Q000201:enzymology* / Q000453:epidemiology*; D008297:Male; D015995:Prevalence; D015203:Reproducibility of Results; D050697:Retinal Dehydrogenase / Q000378:metabolism*; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013737:Testis / Q000201:enzymology*
chemical_list: D015415:Biomarkers; D000080924:Aldehyde Dehydrogenase 1 Family; C545372:ALDH1A2 protein, human; D050697:Retinal Dehydrogenase
keywords: Germ cells; Sertoli cell-only syndrome; retinaldehyde; retinol; spermatogenesis