Susceptibility of gr/gr rearrangements to azoospermia or oligozoospermia is dependent on DAZ and CDY1 gene copy deletions

J Assist Reprod Genet. 2015 Sep;32(9):1333-41. doi: 10.1007/s10815-015-0520-4. Epub 2015 Jul 7.

Abstract

Purpose: 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.

Conclusion: 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.

Keywords: CDY1; DAZ; ICSI; Male infertility; Sperm concentration; gr/gr deletions.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Azoospermia / genetics*
  • Case-Control Studies
  • Chromosome Deletion*
  • Chromosomes, Human, Y / genetics*
  • Deleted in Azoospermia 1 Protein
  • Fertilization in Vitro / methods
  • Follow-Up Studies
  • Gene Deletion*
  • Gene Rearrangement
  • Genetic Diseases, Y-Linked / genetics
  • Genetic Loci
  • Humans
  • Male
  • Nuclear Proteins / genetics*
  • Oligospermia / genetics*
  • Prognosis
  • RNA-Binding Proteins / genetics*
  • Spermatogenesis / genetics

Substances

  • CDY1 protein, human
  • DAZ1 protein, human
  • Deleted in Azoospermia 1 Protein
  • Nuclear Proteins
  • RNA-Binding Proteins