In vitro culture increases the frequency of stochastic epigenetic errors at imprinted genes in placental tissues from mouse concepti produced through assisted reproductive technologies

Eric de Waal, Winifred Mak, Sondra Calhoun, Paula Stein, Teri Ord, Christopher Krapp, Christos Coutifaris, Richard M. Schultz, Marisa S. Bartolomei

Research output: Contribution to journalArticlepeer-review

113 Scopus citations

Abstract

Assisted reproductive technologies (ART) have enabled millions of couples with compromised fertility to conceive children. Nevertheless, there is a growing concern regarding the safety of these procedures due to an increased incidence of imprinting disorders, premature birth, and low birth weight in ART-conceived offspring. An integral aspect of ART is the oxygen concentration used during in vitro development of mammalian embryos, which is typically either atmospheric (∼20%) or reduced (5%). Both oxygen tension levels have been widely used, but 5% oxygen improves preimplantation development in several mammalian species, including that of humans. To determine whether a high oxygen tension increases the frequency of epigenetic abnormalities in mouse embryos subjected to ART, we measured DNA methylation and expression of several imprinted genes in both embryonic and placental tissues from concepti generated by in vitro fertilization (IVF) and exposed to 5% or 20% oxygen during culture. We found that placentae from IVF embryos exhibit an increased frequency of abnormal methylation and expression profiles of several imprinted genes, compared to embryonic tissues. Moreover, IVF-derived placentae exhibit a variety of epigenetic profiles at the assayed imprinted genes, suggesting that these epigenetic defects arise by a stochastic process. Although culturing embryos in both of the oxygen concentrations resulted in a significant increase of epigenetic defects in placental tissues compared to naturally conceived controls, we did not detect significant differences between embryos cultured in 5% and those cultured in 20% oxygen. Thus, further optimization of ART should be considered to minimize the occurrence of epigenetic errors in the placenta.

Original languageEnglish (US)
Article numberArticle 22
JournalBiology of reproduction
Volume90
Issue number2
DOIs
StatePublished - Feb 2014
Externally publishedYes

Keywords

  • Assisted reproductive technologies
  • DNA methylation
  • Epigenetic reprogramming
  • Gene regulation
  • Genomic imprinting
  • In vitro fertilization

ASJC Scopus subject areas

  • Reproductive Medicine

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