title: Alterations of testis-specific promoter methylation in cell-free seminal deoxyribonucleic acid of idiopathic nonobstructive azoospermic men with different testicular phenotypes.
abstract: OBJECTIVE
  To explore the feasibility of quantification of testicular DNA methylation from cell-free seminal DNA (cfsDNA), and analyze promoter methylation alterations in men with idiopathic nonobstructive azoospermia (NOA).
  
  
  METHODS
  Comparison between testicular DNA and paired cfsDNA, and among NOA patients with different testicular phenotypes.
  
  
  METHODS
  Academic research institute and andrology practice.
  
  
  METHODS
  Eighty-eight idiopathic NOA patients with different testicular phenotypes and 24 normozoospermic men.
  
  
  METHODS
  Testicular biopsies and semen analysis.
  
  
  METHODS
  Five testis-specific methylated promoters were selected. Promoter methylation was quantified using MethyLight in testicular DNA and paired cfsDNA, and the mRNA level was determined by real-time quantitative polymerase chain reaction.
  
  
  RESULTS
  Correlations of methylation of the selected five promoters between testicular DNA and paired cfsDNA were observed; and promoter methylation was negatively related to the messenger RNA level in testis. The cfsDNA methylation of these promoters showed different dynamic changes among the subtypes of NOA and normozoospermia. Among them, CCNA1 and DMRT1 promoter methylation in the hypospermatogenesis group was higher than in other groups and showed diagnostic potential for the patient with hypospermatogenesis.
  
  
  CONCLUSIONS
  Cell-free seminal DNA could be a novel, noninvasive biomarker for the detection of testicular epigenetic aberrations. Epigenetic information in cfsDNA related to spermatogenesis may serve to predict successful testicular sperm retrieval in NOA patients.
authors: Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China; Center of Reproductive Medicine, The No.1 Hospital of Wuhan, Wuhan, People's Republic of China.
authors: Chunlin
authors: C
authors: Wu
authors: Center of Reproductive Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors: Xiaofang
authors: X
authors: Ding
authors: Center of Reproductive Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors: Huiping
authors: H
authors: Tan
authors: Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China; Wuhan Tongji Reproductive Medicine Hospital, Wuhan, People's Republic of China. Electronic address: lhgyx@hotmail.com.
authors: Honggang
authors: H
authors: Li
authors: Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China; Wuhan Tongji Reproductive Medicine Hospital, Wuhan, People's Republic of China.
authors: Chengliang
authors: C
authors: Xiong
mesh_terms: D000328:Adult; D053713:Azoospermia / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D001706:Biopsy; D016022:Case-Control Studies; D056750:Cyclin A1 / Q000235:genetics; D004247:DNA / Q000235:genetics*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005240:Feasibility Studies; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011401:Promoter Regions, Genetic; D060888:Real-Time Polymerase Chain Reaction; D055101:Semen Analysis; D013091:Spermatogenesis / Q000235:genetics*; D013094:Spermatozoa / Q000473:pathology; D013737:Testis / Q000737:chemistry* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics; D055815:Young Adult
chemical_list: C503745:CCNA1 protein, human; D056750:Cyclin A1; C110547:DMRT1 protein; D014157:Transcription Factors; D004247:DNA
keywords: Methylation; noninvasive; nonobstructive azoospermia; seminal DNA; testis