High Frequency of Imprinted Methylation Errors in Human Preimplantation Embryos

Sci Rep. 2015 Dec 2:5:17311. doi: 10.1038/srep17311.

Abstract

Assisted reproductive technologies (ARTs) represent the best chance for infertile couples to conceive, although increased risks for morbidities exist, including imprinting disorders. This increased risk could arise from ARTs disrupting genomic imprints during gametogenesis or preimplantation. The few studies examining ART effects on genomic imprinting primarily assessed poor quality human embryos. Here, we examined day 3 and blastocyst stage, good to high quality, donated human embryos for imprinted SNRPN, KCNQ1OT1 and H19 methylation. Seventy-six percent day 3 embryos and 50% blastocysts exhibited perturbed imprinted methylation, demonstrating that extended culture did not pose greater risk for imprinting errors than short culture. Comparison of embryos with normal and abnormal methylation didn't reveal any confounding factors. Notably, two embryos from male factor infertility patients using donor sperm harboured aberrant methylation, suggesting errors in these embryos cannot be explained by infertility alone. Overall, these results indicate that ART human preimplantation embryos possess a high frequency of imprinted methylation errors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blastocyst / metabolism*
  • DNA Methylation*
  • Female
  • Fertilization in Vitro / adverse effects*
  • Genomic Imprinting*
  • Humans
  • Male
  • Potassium Channels, Voltage-Gated / genetics
  • Potassium Channels, Voltage-Gated / metabolism
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • snRNP Core Proteins / genetics
  • snRNP Core Proteins / metabolism

Substances

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