Placental abnormalities in mouse embryos lacking the orphan nuclear receptor ERR-beta

Nature. 1997 Aug 21;388(6644):778-82. doi: 10.1038/42022.


Classical endocrine studies have shown that steroid hormones are required for the maintenance of pregnancy and placental viability. The oestrogen-receptor-related receptor beta (ERR-beta) is an orphan member of the superfamily of nuclear hormone receptors. Although ERR-beta is homologous to the oestrogen receptor and binds the oestrogen response element, it is not activated by oestrogens. Expression of ERR-beta during embryogenesis defines a subset of extra-embryonic ectoderm that subsequently forms the dome of the chorion, suggesting that ERR-beta may be involved in early placental development. Homozygous mutant embryos generated by targeted disruption of the Estrrb gene have severely impaired placental formation, and die at 10.5 days post-coitum. The mutants display abnormal chorion development associated with an overabundance of trophoblast giant cells and a severe deficiency of diploid trophoblast. The phenotype can be rescued by aggregation of Estrrb mutant embryos with tetraploid wild-type cells, which contribute exclusively to extra-embryonic tissues. Our results indicate that ERR-beta has an important role in early placentation, and suggest that an inductive signal originating from or modified by the chorion is required for normal trophoblast proliferation and differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chorion / abnormalities
  • Embryonic and Fetal Development / genetics
  • Female
  • Fetal Death / genetics
  • Gene Expression
  • Gene Targeting
  • Male
  • Mice
  • Placenta / abnormalities*
  • Placenta / embryology
  • Receptors, Estrogen / deficiency
  • Receptors, Estrogen / physiology*
  • Stem Cells
  • Trophoblasts / cytology
  • Trophoblasts / metabolism


  • Receptors, Estrogen
  • estrogen receptor-related receptor beta

Associated data

  • GENBANK/AF022222