title: Susceptibility of gr/gr rearrangements to azoospermia or oligozoospermia is dependent on DAZ and CDY1 gene copy deletions.
abstract: OBJECTIVE
  The purpose of this study was to determine the association of AZFc subdeletions (gr/gr, b1/b3 and b2/b3) and deletion of DAZ and CDY1 gene copies with male infertility
  
  
  METHODS
  Three hundred twelve controls, 172 azoospermic and 343 oligozoospermic subjects were subjected to AZFc subdeletion typing by STS PCR. Deletion of DAZ and CDY1 gene copies was done using sequence family variant analysis. Sperm concentration and motility were compared between men with and without AZFc subdeletions. Effect of the AZFc subdeletions on ICSI outcome was evaluated.
  
  
  RESULTS
  Amongst the three AZFc subdeletions, the frequency of gr/gr was higher in oligozoospermic (10.5 %) and azoospermic (11.6 %) men as compared to controls (5.1 %). In men with AZFc subdeltions, loss of two DAZ and one CDY1 gene copy made them highly susceptible to azoospermia and severe oligozoospermia with OR of 29.7 and 26, respectively. These subdeletions had no effect on ICSI outcome, albeit there were an increased number of poor quality embryos in AZFc subdeleted group.
  
  
  CONCLUSIONS
  AZFc subdeletions are a major risk factor for male infertility in the Indian population. In the subjects with AZFc subdeletions, the deletion of DAZ and CDY1 gene copies increases its susceptibility to azoospermia or severe oligozoospermia. Since these deletions can be vertically transmitted to the future male offspring by ICSI, it will be essential to counsel the couples for the transmission of the genetic defect in the male offspring born after assisted reproduction and the risk of perpetuating infertility in future generation.
authors.affiliation: Molecular and Cellular Biology Laboratory, National Institute for Research in Reproductive Health (ICMR), J. M. Street, Parel, Mumbai, 400012, India.
authors.forename: S
authors.initials: S
authors.lastname: Sen
authors.affiliation: Human Genetic Division, Department of Anatomy, Mahatma Gandhi Institute of Medical Sciences, Sevagram, 442102, Wardha, India.
authors.forename: P
authors.initials: P
authors.lastname: Ambulkar
authors.affiliation: Hinduja IVF Centre, PD Hinduja Hospital and Medical Research Center, Veer Savarkar Marg, Mahim, Mumbai, 400016, India.
authors.forename: I
authors.initials: I
authors.lastname: Hinduja
authors.affiliation: Hinduja IVF Centre, PD Hinduja Hospital and Medical Research Center, Veer Savarkar Marg, Mahim, Mumbai, 400016, India.
authors.forename: K
authors.initials: K
authors.lastname: Zaveri
authors.affiliation: Department of Reproductive Endocrinology and Infertility, National Institute for Research in Reproductive Health (ICMR), J. M. Street, Parel, Mumbai, 400012, India.
authors.forename: J
authors.initials: J
authors.lastname: Gokral
authors.affiliation: Human Genetic Division, Department of Anatomy, Mahatma Gandhi Institute of Medical Sciences, Sevagram, 442102, Wardha, India.
authors.forename: A
authors.initials: A
authors.lastname: Pal
authors.affiliation: Molecular and Cellular Biology Laboratory, National Institute for Research in Reproductive Health (ICMR), J. M. Street, Parel, Mumbai, 400012, India. deepaknmodi@yahoo.com.
authors.forename: D
authors.initials: D
authors.lastname: Modi
mesh_terms: D000328:Adult; D053713:Azoospermia / Q000235:genetics*; D016022:Case-Control Studies; D002872:Chromosome Deletion; D041322:Chromosomes, Human, Y / Q000235:genetics*; D000075364:Deleted in Azoospermia 1 Protein; D005307:Fertilization in Vitro / Q000379:methods; D005500:Follow-Up Studies; D017353:Gene Deletion; D015321:Gene Rearrangement; D050174:Genetic Diseases, Y-Linked / Q000235:genetics; D056426:Genetic Loci; D006801:Humans; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D009845:Oligospermia / Q000235:genetics*; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000235:genetics*; D013091:Spermatogenesis / Q000235:genetics
chemical_list: C118459:CDY1 protein, human; C095668:DAZ1 protein, human; D000075364:Deleted in Azoospermia 1 Protein; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins
keywords: CDY1; DAZ; ICSI; Male infertility; Sperm concentration; gr/gr deletions