Blockade of erythropoietin signal at the early postimplantation period inhibits the development of decidua and embryo in mice.

Abstract

We have previously shown that erythropoietin and erythropoietin receptor mRNAs are expressed in mouse embryos and in decidua at the early postimplantation stage, and that erythropoietin receptor mRNA is expressed in advance of erythropoietin mRNA. We subsequently studied the role of exogenous erythropoietin in early development until the embryo proper can express erythropoietin by itself. In the present study, to block the erythropoietin signal in the decidual body where the early postimplantation embryo develops with decidua, we injected an antierythropoietin antibody or soluble erythropoietin receptor into decidual bodies through the uterine wall at day 6 of gestation. For controls, we injected saline or denatured soluble erythropoietin receptor. After 3 or 4 days, we examined the experimental and control decidual bodies. Macroscopic examinations revealed that experimental groups showed anemic small decidua in 50-60% of the decidual bodies of which 18-25% contained developmental-arrested embryos with brain anomalies. Immunohistochemical examination revealed that positive erythropoietin receptor immunoreactivity was detected in the sinusoidal linings of the decidua capsularis and the neuroepithelial cells of the embryos in the controls, while in the experimental groups, these erythropoietin receptor-positive cells were destroyed leading to few erythrocytes in the decidua, and lacy neuroepithelium of the embryos due to apoptosis. In conclusion, erythropoietin from maternal blood appears to be required for sinusoids to retain maternal blood, and for neurogenesis in embryos during a short period of mouse development.