Copy number variants in patients with severe oligozoospermia and Sertoli-cell-only syndrome

PLoS One. 2011 Apr 29;6(4):e19426. doi: 10.1371/journal.pone.0019426.


A genetic origin is estimated in 30% of infertile men with the common phenotypes of oligo- or azoospermia, but the pathogenesis of spermatogenic failure remains frequently obscure. To determine the involvement of Copy Number Variants (CNVs) in the origin of male infertility, patients with idiopathic severe oligozoospermia (N = 89), Sertoli-cell-only syndrome (SCOS, N = 37)) and controls with normozoospermia (N = 100) were analysed by array-CGH using the 244A/400K array sets (Agilent Technologies). The mean number of CNVs and the amount of DNA gain/loss were comparable between all groups. Ten recurring CNVs were only found in patients with severe oligozoospermia, three only in SCOS and one CNV in both groups with spermatogenic failure but not in normozoospermic men. Sex-chromosomal, mostly private CNVs were significantly overrepresented in patients with SCOS. CNVs found several times in all groups were analysed in a case-control design and four additional candidate genes and two regions without known genes were associated with SCOS (P<1×10(-3)). In conclusion, by applying array-CGH to study male infertility for the first time, we provide a number of candidate genes possibly causing or being risk factors for the men's spermatogenic failure. The recurring, patient-specific and private, sex-chromosomal CNVs as well as those associated with SCOS are candidates for further, larger case-control and re-sequencing studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Azoospermia / genetics*
  • Case-Control Studies
  • Chromosome Deletion
  • Chromosomes, Human, X / genetics
  • Comparative Genomic Hybridization
  • Gene Dosage*
  • Humans
  • Infertility, Male / genetics*
  • Male
  • Middle Aged
  • Oligospermia / genetics*
  • Phenotype
  • Sequence Analysis, DNA
  • Sertoli Cell-Only Syndrome / genetics*
  • Spermatogenesis / genetics