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Epidermal growth factor-like ligands and erbB genes in the peri-implantation rabbit uterus and blastocyst
T Klonisch1, P Wolf, S Hombach-Klonisch
1Department of Anatomy and Cell Biology, Faculty of Medicine, Martin Luther University, D-06097 Halle/Saale, Germany. thomas.klonisch@medizin.uni-halle.de
Abstract:
Molecular cloning of the partial cDNA coding sequences of the four erbB receptors and the epidermal growth factor (EGF)-like ligands EGF, transforming growth factor alpha (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 the rabbit. Employing nonradioactive in situ hybridization and immunolocalization, we observed differential expression of erbB1-erbB3 within the trophectoderm of the blastocyst. ErbB1 was strongly expressed in the cytotrophoblast but was downregulated upon syncytium formation. ErbB3 was a product of both the cyto- and syncytiotrophoblast. Despite the expression of erbB2 mRNA, the trophectoderm was devoid of immunoreactive ErbB2. ErbB4 gene activity 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. In the peri-implantation period, gene activities of erbB1-erbB3 were upregulated upon decidualization. At the site of implantation, uterine luminal epithelial cells apposing the preimplantation blastocyst displayed a distinct membrane immunolocalization of ErbB2, identifying the uterine epithelium as target for EGF, TGFalpha, and HB-EGF derived from both the embryonic trophectoderm and the uterine epithelium. In the luminal epithelium at the antimesometrial uterine site, HB-EGF gene activity was upregulated at the time of blastocyst attachment, but this upregulation was not reflected in an increase in immunoreactive HB-EGF. The detection of tyrosine phosphorylated ErbB2 in the rabbit placenta indicated the presence of a functional ErbB/EGF-like system in the pregnant rabbit uterus. This study provides strong evidence for a role of the ErbB/EGF-like system in embryo/maternal interactions during the peri-implantation period in the rabbit.
Insights
The epidermal growth factor (EGF) receptor/ligand system is crucial for embryo-maternal interactions during rabbit implantation. This study maps the expression of key EGF receptors (ErbB1-3) and ligands (EGF, TGFα, HB-EGF) in the uterus and blastocyst.
Area of Science:
- Reproductive biology
- Molecular and cellular biology
- Developmental biology
Background:
- The epidermal growth factor (EGF) receptor/ligand system plays a vital role in cellular communication and development.
- Understanding the spatiotemporal expression of this system is crucial for elucidating embryo-maternal interactions during early pregnancy.
Purpose of the Study:
- To comprehensively analyze the expression patterns of the EGF receptor/ligand system during the peri-implantation period in rabbits.
- To investigate the role of this system in mediating interactions between the embryo and the maternal uterus.
Main Methods:
- Molecular cloning of partial cDNA sequences for four erbB receptors and three EGF-like ligands.
- Nonradioactive in situ hybridization and immunolocalization techniques were employed.
- Analysis of gene and protein expression in the rabbit blastocyst and uterus during different reproductive states.
Main Results:
- Differential expression of erbB1-erbB3 was observed in the trophectoderm of the blastocyst, with specific patterns during cytotrophoblast and syncytium formation.
- ErbB1-erbB3 were expressed in the nonpregnant, pseudopregnant, and pregnant rabbit uterus, with upregulation upon decidualization.
- ErbB2 was localized to uterine luminal epithelial cells at implantation sites, suggesting a role as a target for embryonic and uterine-derived EGF-like ligands.
- Tyrosine phosphorylated ErbB2 was detected in the rabbit placenta, confirming a functional ErbB/EGF-like system.
Conclusions:
- The ErbB/EGF-like system is dynamically expressed in both the peri-implantation blastocyst and the maternal uterus.
- This system is implicated in critical embryo-maternal communication and interactions during rabbit implantation.
- The findings provide strong evidence for the involvement of the ErbB/EGF-like system in successful pregnancy establishment.