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

• DOI: 10.1038/42022
• Publication Date: 2002-07-26T08:37:10Z
• Authors: Jiangming Luo; Robert Sladek; Jo-Ann Bader; Annie Matthyssen; Janet Rossant; Vincent Giguère
• Keywords: Male; 0303 health sciences; Placenta; Stem Cells; Gene Expression; Chorion; Trophoblasts; Embryonic and Fetal Development; Mice; 03 medical and health sciences; Receptors, Estrogen; Gene Targeting; Animals; Female; Fetal Death

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.