Semen samples showing an increased rate of spermatozoa with imprinting errors have a negligible effect in the outcome of assisted reproduction techniques

Epigenetics. 2012 Oct;7(10):1115-24. doi: 10.4161/epi.21743. Epub 2012 Aug 13.


The topic of imprinting defects present in the sperm of infertile patients has been addressed by several reports in the last few years. However, whether methylation abnormalities at one or few CpGs within an imprinted locus are pathological is a matter of debate. Moreover, whether imprinting anomalies in sperm could interfere with fertility treatment outcomes is still unknown. In this report we analyze the sperm DNA methylation profile of H19-ICR, KvDMR, SNRPN-ICR, IG-DMR and MEG3-DMR by pyrosequencing in 107 infertile men series and a control population of 30 proven fertile males. DNA methylation was statistically evaluated from two points of view: first, the methylation of each CpG was analyzed in the control population and the mean, standard deviation and range were determined and compared with infertile population data; second, in order to define altered methylation patterns for each region, a hierarchical cluster analysis was performed by which individuals were grouped in different clusters according to the degree of similarity of their methylation pattern. Two pieces of data supported the results obtained in the multi-variate analysis: the classification of the vast majority of control individuals in clusters with normal methylation patterns and the significant differences in methylation levels found between individuals within the normal and abnormal clusters. Individuals included in normal and abnormal methylation clusters were compared according to seminal parameters as well as to the outcome of assisted reproduction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CpG Islands / genetics
  • DNA Methylation / genetics*
  • Genomic Imprinting*
  • Humans
  • Infertility, Male* / genetics
  • Infertility, Male* / pathology
  • Male
  • Potassium Channels, Voltage-Gated / genetics
  • RNA, Long Noncoding / genetics
  • Reproductive Techniques, Assisted
  • Semen* / cytology
  • Semen* / metabolism
  • Spermatozoa* / cytology
  • Spermatozoa* / metabolism
  • snRNP Core Proteins / genetics


  • H19 long non-coding RNA
  • KCNQ1OT1 long non-coding RNA, human
  • MEG3 non-coding RNA, human
  • Potassium Channels, Voltage-Gated
  • RNA, Long Noncoding
  • SNRPN protein, human
  • snRNP Core Proteins