Selective loss of imprinting in the placenta following preimplantation development in culture

Development. 2004 Aug;131(15):3727-35. doi: 10.1242/dev.01241. Epub 2004 Jul 7.

Abstract

Preimplantation development is a period of dynamic epigenetic change that begins with remodeling of egg and sperm genomes, and ends with implantation. During this time, parental-specific imprinting marks are maintained to direct appropriate imprinted gene expression. We previously demonstrated that H19 imprinting could be lost during preimplantation development under certain culture conditions. To define the lability of genomic imprints during this dynamic period and to determine whether loss of imprinting continues at later stages of development, imprinted gene expression and methylation were examined after in vitro preimplantation culture. Following culture in Whitten's medium, the normally silent paternal H19 allele was aberrantly expressed and undermethylated. However, only a subset of individual cultured blastocysts (approximately 65%) exhibited biallelic expression, while others maintained imprinted H19 expression. Loss of H19 imprinting persisted in mid-gestation conceptuses. Placental tissues displayed activation of the normally silent allele for H19, Ascl2, Snrpn, Peg3 and Xist while in the embryo proper imprinted expression for the most part was preserved. Loss of imprinted expression was associated with a decrease in methylation at the H19 and Snrpn imprinting control regions. These results indicate that tissues of trophectoderm origin are unable to restore genomic imprints and suggest that mechanisms that safeguard imprinting might be more robust in the embryo than in the placenta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Autoantigens
  • Blastocyst / cytology
  • Blastocyst / physiology*
  • Cells, Cultured
  • DNA Methylation
  • Female
  • Genomic Imprinting*
  • Gestational Age
  • Kruppel-Like Transcription Factors
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Placenta / metabolism
  • Placenta / physiology*
  • Pregnancy
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • RNA, Long Noncoding
  • RNA, Untranslated / genetics*
  • RNA, Untranslated / metabolism
  • Ribonucleoproteins, Small Nuclear / genetics
  • Ribonucleoproteins, Small Nuclear / metabolism
  • Sex Chromosomes
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • snRNP Core Proteins

Substances

  • Autoantigens
  • H19 long non-coding RNA
  • Kruppel-Like Transcription Factors
  • PEG3 protein, human
  • Peg3 protein, mouse
  • RNA, Long Noncoding
  • RNA, Untranslated
  • Ribonucleoproteins, Small Nuclear
  • Transcription Factors
  • XIST non-coding RNA
  • snRNP Core Proteins
  • Protein Kinases