title: Dysregulation of apoptotic pathway candidate genes and proteins in infertile azoospermia patients.
abstract: OBJECTIVE
  To dissect the role of the apoptotic pathway and its regulation in the pathogenesis of male infertility in nonobstructive azoospermia.
  
  
  METHODS
  Prospective study.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  Sixty-three infertile azoospermic patients with different histologic phenotypes were recruited (obstructive azoospermia, n = 16; hypospermatogenesis, n = 11; maturation arrest, n = 15; Sertoli cell only, n = 21).
  
  
  METHODS
  Testicular biopsies for histopathologic and expression analysis.
  
  
  METHODS
  Expression analysis by quantitative reverse transcription-polymerase chain reaction, protein localization by immunohistochemistry and apoptotic proteome array.
  
  
  RESULTS
  Results showed significantly increased expression of proapoptotic proteins like BAX, BAD, and BAK and comparatively lowered expression of antiapoptotic BCL2 and BCLW. Immunostaining revealed increased active caspase-3 activity and more TUNEL-positive cells in different impaired phenotypes as compared with normal. In addition, significantly increased m-RNA expression of TGFB1, P53, and FASLG along with significant down-regulation of VEGFA were observed. Expression of phosphorylated P53 at the S15 position and phosphorylated RAD17 at S635 was observed in cases with spermatogenic impairment at the translational level.
  
  
  CONCLUSIONS
  The results clearly indicate increased levels of apoptosis along with its other regulatory factors. The balance between pro- (BAX and BAK) and antiapoptotic (BCL2 and BCLW) genes was disturbed, which may lead to altered apoptosis. Therefore, altered regulation of apoptosis might be associated with impaired spermatogenesis, eventually leading to male infertility.
authors.affiliation: Department of Molecular and Human Genetics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
authors.forename: Deepika
authors.initials: D
authors.lastname: Jaiswal
authors.affiliation: Department of Urology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
authors.forename: Sameer
authors.initials: S
authors.lastname: Trivedi
authors.affiliation: Department of Endocrinology and Metabolism, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
authors.forename: Neeraj K
authors.initials: NK
authors.lastname: Agrawal
authors.affiliation: Department of Molecular and Human Genetics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. Electronic address: skiran@bhu.ac.in.
authors.forename: Kiran
authors.initials: K
authors.lastname: Singh
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000032:analysis / Q000235:genetics*; D053713:Azoospermia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001706:Biopsy; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D011446:Prospective Studies; D040901:Proteomics / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000737:chemistry* / Q000473:pathology; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; D012333:RNA, Messenger
keywords: Apoptosis; damage; infertility; spermatogenesis; testis