Epidermal growth factor-like ligands and erbB genes in the peri-implantation rabbit uterus and blastocyst

Molecular cloning of the partial cDNA coding sequences of the four erbB rec eptors and the epidermal growth factor (EGF)-like ligands EGF, transforming growth factor or (TGF), and heparin-binding EGF (HB-EGF) has provided the basis for a comprehensive analysis of the spatiotemporal expression pattern of the EGF receptor/ligand system during the peri-implantation period in t he rabbit. Employing nonradioactive in situ hybridization and immunolocaliz ation, we observed differential expression of erbB1-erbB3 within the trophe ctoderm of the blastocyst. ErbB1 was strongly expressed in the cytotrophobl ast but was downregulated upon syncytium formation. ErbB3 was a product of both the cyto- and syncytiotrophoblast. Despite the expression of erbB2 mRN A, the trophectoderm was devoid of immunoreactive ErbB2. ErbB4 gene activit y was exclusively detected in the trophoblast at midpregnancy. The luminal and glandular epithelium and stroma of the nonpregnant, pseudopregnant, and pregnant rabbit uterus at Day 6 of gestation also expressed ErbB1-ErbB3. I n the peri-implantation period, gene activities of erbB1-erbB3 were upregul ated upon decidualization. At the site of implantation, uterine luminal epi thelial cells apposing the preimplantation blastocyst displayed a distinct membrane immunolocalization of ErbB2, identifying the uterine epithelium as target for EGF, TGF alpha, and HB-EGF derived from both the embryonic trop hectoderm and the uterine epithelium. In the luminal epithelium at the anti mesometrial uterine site, HB-EGF gene activity was upregulated at the time of blastocyst attachment, but this upregulation was not reflected in an inc rease in immunoreactive HB-EGF. The detection of tyrosine phosphorylated Er bB2 in the rabbit placenta indicated the presence of a functional ErbB/EGF- like system in the pregnant rabbit uterus. This study provides strong evide nce for a role of the ErbB/EGF-like system in embryo/maternal interactions during the peri-implantation period in the rabbit.