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Placental abnormalities in mouse embryos lacking the orphan nuclear receptor ERR-beta
1Molecular Oncology Group, Royal Victoria Hospital, Montreal, Québec, Canada.
Abstract:
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.
Insights
Estrogen-related receptor beta (ERR-beta) is crucial for early placental development. Its absence impairs chorion formation and leads to embryonic death, highlighting its role in trophoblast regulation.
Area of Science:
- Endocrinology
- Developmental Biology
- Genetics
Background:
- Steroid hormones are vital for pregnancy maintenance and placental viability.
- Estrogen-related receptor beta (ERR-beta) is a nuclear hormone receptor homologous to the estrogen receptor but not activated by estrogens.
- ERR-beta expression in embryogenesis marks cells forming the chorion, suggesting a role in placental development.
Purpose of the Study:
- To investigate the role of ERR-beta in early placental development.
- To understand the function of ERR-beta in chorion formation and trophoblast differentiation.
Main Methods:
- Targeted gene disruption of the Estrogen-related receptor beta (ERR-beta) gene (Estrrb) in mice.
- Analysis of homozygous mutant embryos for placental and chorion development.
- Rescue experiments using aggregation of mutant embryos with tetraploid wild-type cells.
Main Results:
- Homozygous Estrrb mutant embryos exhibit severely impaired placental formation and die at 10.5 days post-coitum.
- Mutants show abnormal chorion development with an excess of trophoblast giant cells and a deficit of diploid trophoblast.
- Aggregation with tetraploid wild-type cells rescued the mutant phenotype, indicating ERR-beta's role in extra-embryonic tissues.
Conclusions:
- Estrogen-related receptor beta (ERR-beta) plays a critical role in early placentation.
- Chorion development regulated by ERR-beta is essential for normal trophoblast proliferation and differentiation.
- An inductive signal from the chorion is necessary for proper placental development.