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Aberrant DNA methylation at imprinted genes in testicular sperm retrieved from men with obstructive azoospermia and undergoing vasectomy reversal.

Abstract
Male factor infertility has been associated with abnormal DNA methylation at imprinted genes. Little information is available on the status of imprinting in the sperm of men with azoospermia, including the association between aberrant imprinting and obstructive azoospermia (OA) or non-OA (NOA). Analysis of DNA methylation at imprinted genes in the sperm of men undergoing vasectomy reversal would aid determination of whether aberrant imprinting is associated with obstruction. Testicular sperm was retrieved from testicular biopsies obtained from men with azoospermia (N=18), including OA (N=10), NOA (N=5), and unknown pathology (N=3), and from men undergoing vasectomy reversal (N=17). Sperm was also obtained from proven fertile men (N=9). DNA methylation was investigated at multiple CpG sites within the differentially methylated regions (DMRs) of three imprinted genes, H19, IG-GTL2 and MEST, using bisulphite sequencing. Unique clones representative of single cells were analyzed. We found a significant decrease in DNA methylation at the H19 DMR in testicular sperm of azoospermic men compared with proven fertile men. The decrease was also significant between OA and proven fertile men, and between men undergoing vasectomy reversal and proven fertile men, suggesting that aberrant DNA methylation may be associated with obstruction. Changes in DNA methylation at IG-GTL2 and MEST DMRs among groups were not significant. Our data suggest that imprinting abnormalities may be associated with obstruction and may occur in response to changes in testicular environment and not only spermatogenesis failure, as previously reported. Methylation at the H19 DMR was particularly prone to modification in testicular sperm.
AuthorsAgata Minor, Victor Chow, Sai Ma
JournalReproduction (Cambridge, England) (Reproduction) Vol. 141 Issue 6 Pg. 749-57 (Jun 2011) ISSN: 1741-7899 [Electronic] England
PMID21389080 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • H19 long non-coding RNA
  • MEG3 non-coding RNA, human
  • Proteins
  • RNA, Long Noncoding
  • RNA, Untranslated
  • mesoderm specific transcript protein
Topics
  • Adult
  • Azoospermia (genetics, pathology, physiopathology)
  • Biopsy
  • British Columbia
  • CpG Islands
  • DNA Methylation
  • Fertility (genetics)
  • Gene Expression Regulation, Developmental
  • Genomic Imprinting
  • Humans
  • Male
  • Middle Aged
  • Proteins (genetics)
  • RNA, Long Noncoding
  • RNA, Untranslated (genetics)
  • Spermatogenesis (genetics)
  • Spermatozoa (metabolism, pathology)
  • Vasovasostomy

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