Epidermal Growth Factor-Like Ligands and erbB Genes in the Peri-Implantation Rabbit Uterus and Blastocyst1

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.

Expression of SWAP-70 in the uterus and feto-maternal interface during embryonic implantation and pregnancy in the rhesus monkey (Macaca mulatta)

“…It remains unclear which factors are the upstream stimulating molecules of SWAP-70-involved signaling pathway in primate trophoblasts during implantation. Many growth factors with tyrosine kinase receptors that are produced by uterine endometrium or embryo itself, such as epidermal growth factor, transforming growth factor alpha, insulin-like growth factor, etc have been proven by a large number of previous studies to play important roles in regulation of feto-maternal interaction and trophoblast invasion during embryonic implantation (Chia et al 1995;Klonisch et al 2001;Boomsma et al 2003). They might be the candidates that regulate trophoblast migration through Rac GTPase activated by SWAP-70.…”

HB-EGF: A unique mediator of embryo-uterine interactions during implantation

“…In rabbits, day 7 of pregnancy is considered the time of blastocyst attachment. HB-EGF mRNA is induced at the antimesometrial side of the uterus where the attachment reaction occurs on day 7 [38]. ErbBs exhibit differential expression patterns in trophoblast cells, but understanding roles of HB-EGF and ErbBs in rabbit endometria and embryos will require further investigation.…”

Expression Levels of EGF, TGF-α, and EGF-R Are Significantly Reduced in Pre-Implantation Cloned Mouse Embryos

“…Previous studies have revealed transcripts for this growth factor in embryos of several species, including human (Klonisch et al, 2001), bovine (Chia et al, 1995;Kobayashi et al, 1994), porcine (Singh et al, 1993) and mouse (Das et al, 1991;Harada et al, 1997). EGF mRNA is rapidly down-regulated in mouse embryos (Das et al, 1991;Moller et al, 2001), suggesting that although detection in zygotes is due to internalization of maternal EGF during oogenesis, IVF-derived and cloned embryos are capable of expressing EGF independent of maternal influence (Kidder, 1992;Wiley et al, 1992).…”