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

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.