Placental abnormalities in mouse embryos lacking the orphan nuclear receptor ERR-beta.
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.
Luo
J
J
Molecular Oncology Group, Royal Victoria Hospital, Montreal, Québec, Canada.
Sladek
R
R
Bader
J A
JA
Matthyssen
A
A
Rossant
J
J
Giguère
V
V
D000818:Animals; D002823:Chorion / Q000002:abnormalities; D005314:Embryonic and Fetal Development / Q000235:genetics; D005260:Female; D005313:Fetal Death / Q000235:genetics; D015870:Gene Expression; D018390:Gene Targeting; D008297:Male; D051379:Mice; D010920:Placenta / Q000002:abnormalities* / Q000196:embryology; D011960:Receptors, Estrogen / Q000172:deficiency / Q000502:physiology*; D013234:Stem Cells; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism
D011960:Receptors, Estrogen; C107914:estrogen receptor-related receptor beta