Loss of PGC-specific expression of the orphan nuclear receptor ERR-β results in reduction of germ cell number in mouse embryos

Estrogen related receptor beta (ERR-β) is an orphan nuclear receptor specifically expressed in a subset of extra-embryonic ectoderm of post-implantation embryos. ERR-β is essential for placental development since the ERR-β null mutants die at 10.5 dpc due to the placenta abnormality. Here, we show that the ERR-β is specifically expressed in primordial germ cells (PGC), obviously another important cell type for reproduction. Expression of the ERR-β mRNA in embryonic germ cells started at E11.5 as soon as PGC reached genital ridges, and persisted until E15–E16 in both sexes. Immunostaining with anti-ERR-β antibody revealed that the ERR-β protein is exclusively expressed in germ cells in both male and female gonads from E11.5 to E16. 5. To study function of the ERR-β in PGC, we complemented placental defects of the ERR-β null mutants with wild-type tetraploid embryos, and analyzed germ cell development in the rescued embryos. It was found that development of gonad and PGC was not apparently affected, but number of germ cells was significantly reduced in male and female gonads, suggesting that the ERR-β appears to be involved in proliferation of gonadal germ cells. The rescued embryos could develop to term and grow up to adulthood. The rescued ERR-β null male were found to be fertile, but both male and female null mutants exhibited behavioural abnormalities, implying that the ERR-β plays important roles in wider biological processes than previously thought.