Epidermal growth factor receptor and ligands in elongating bovine blastocysts

Kliem, Anne; Tetens, Frank; Klonisch, Thomas; Grealy, Maura; Fischer, Bernd

doi:10.1002/(sici)1098-2795(199812)51:4<402::aid-mrd7>3.0.co;2-9

Cited by 36 publications

(14 citation statements)

References 48 publications

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“…Various growth factors (bFGF, TGF-α, TGF-β 2 PDGF-A, IGF-I, IGF-II) and growth factor receptors (Insulin-R, IGF-IR, IGF-IIR, PDGF-Rα) have been detected in early bovine embryos on the mRNA (Watson et al 1992) and protein level (Kim and Fischer 1997;Kliem et al 1998a). TGF-β, bFGF and insulin play an essential role in the development of bovine embryos in vitro (Larson et al 1990;Seidel et al 1991).…”

Section: Discussionmentioning

confidence: 99%

“…In CD-1 mice, the mutants lived for up to 3 weeks and showed skin, kidney, brain, liver and gastrointestinal tract abnormalities. We have demonstrated the presence of the EGF-R and its ligands EGF, TGF-α and heparin-binding EGF-like growth factor (HB-EGF) in the bovine preimplantation embryo before and after the onset of elongation (Kliem et al 1998a). The present study was performed to investigate potential candidates of the EGF signal transduction pathway in bovine blastocysts.…”

Section: Introductionmentioning

confidence: 99%

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Expression of proto-oncogenes in bovine preimplantation blastocysts

Tetens¹,

Kliem²,

Tscheudschilsuren³

et al. 2000

Anatomy and Embryology

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Proto-oncogenes are involved in the regulation of gene expression, for example after ligand binding to growth factor receptors. Expression of the proto-oncogenes c-fos, c-jun, c-ha-ras and c-myc was studied in in vivo grown and in vitro cultured bovine preimplantation blastocysts employing RT-PCR, ribonuclease protection assay and immunohistochemistry. Thirteen- and 14- day-old preimplantation blastocysts, i.e. stages before and during trophoblast elongation, were used. In in vivo-grown blastocysts c-fos, c-jun and c-ha-ras transcripts as well as c-Fos, c-Jun and c-Myc proteins were detected in all stages studied. Cultured blastocysts were treated with 10 nM epidermal growth factor and 10 nM transforming growth factor-alpha simultaneously. Epidermal growth factor and transforming growth factor-alpha treatment induced c-fos mRNA and c-Myc protein expression. The induction of downstream targets of the epidermal growth factor receptor by epidermal growth factor and transforming growth factor-alpha indicates a functional epidermal growth factor signal transduction pathway in elongating bovine blastocysts.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Expression of proto-oncogenes in bovine preimplantation blastocysts

Tetens¹,

Kliem²,

Tscheudschilsuren³

et al. 2000

Anatomy and Embryology

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“…Therefore, both EGF and TGFa appear to be essential in early embryonic development in ruminant species. In the mouse and porcine embryo, EGF and TGFa are localized in trophoblast and are considered to have both autocrine and paracrine functions that are involved in elongation of the embryo (Dardik et al 1992, Vaughan et al 1992, Kliem et al 1998. Thus, all the factors alluded to above may participate in the initial elongation of the bovine embryo.…”

Section: Blastocyst To Tubular Periodmentioning

confidence: 99%

Blastocyst elongation, trophoblastic differentiation, and embryonic pattern formation

Blomberg¹,

Hashizume²,

Viebahn³

2008

Reproduction

106

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The molecular basis of ungulate and non-rodent conceptus elongation and gastrulation remains poorly understood; however, use of stateof-the-art genomic technologies is beginning to elucidate the mechanisms regulating these complicated processes. For instance, transcriptome analysis of elongating porcine concepti indicates that protein synthesis and trafficking, cell growth and proliferation, and cellular morphology are major regulated processes. Furthermore, potential autocrine roles of estrogen and interleukin-1-b in regulating porcine conceptus growth and remodeling and metabolism have become evident. The importance of estrogen in pig is emphasized by the altered expression of essential steroidogenic and trophoblast factors in lagging ovoid concepti. In ruminants, the characteristic mononucleate trophoblast cells differentiate into a second lineage important for implantation, the binucleate trophoblast, and transcriptome profiling of bovine concepti has revealed a gene cluster associated with rapid trophoblast proliferation and differentiation. Gene cluster analysis has also provided evidence of correlated spatiotemporal expression and emphasized the significance of the bovine trophoblast cell lineage and the regulatory mechanism of trophoblast function. As a part of the gastrulation process in the mammalian conceptus, specification of the germ layers and hence definitive body axes occur in advance of primitive streak formation. Processing of the transforming growth factor-b-signaling molecules nodal and BMP4 by specific proteases is emerging as a decisive step in the initial patterning of the pre-gastrulation embryo. The topography of expression of these and other secreted molecules with reference to embryonic and extraembryonic tissues determines their local interaction potential. Their ensuing signaling leads to the specification of axial epiblast and hypoblast compartments through cellular migration and differentiation and, in particular, the specification of the early germ layer tissues in the epiblast via gene expression characteristic of endoderm and mesoderm precursor cells.

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“…The elongating bovine blastocyst expresses EGF-R, EGF, TGF-alpha, and HB-EGF. Further, at day 13 of gestation, the expression of EGF-R, EGF, and TGF-alpha could be detected in the bovine endometrium (Kliem et al, 1998). It has been shown that EGF and TGFalpha stimulate the proliferation of mouse uterine epithelial cells in vitro and, additionally, directly promote trophoblast development (Machida et al, 1995).…”

Section: Epidermal Growth Factormentioning

confidence: 98%

2 Identification of Genes Induced by the Conceptus in the Bovine Endometrium During the Pre-Implantation Period

Klein¹,

Bauersachs²,

Ulbrich³

et al. 2006

Reprod. Fertil. Dev.

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Early embryonic development, implantation, and maintenance of a pregnancy are critically dependent on an intact embryo-maternal communication. So far, only few signals involved in this dialogue have been identified. In ruminants, interferon tau (IFN�) plays a key role in the process of maternal recognition of pregnancy by exhibiting antiluteolytic activity. Even though many experimental findings indicate a pivotal role of IFN� in the context of embryo-maternal communication in ruminants, a number of other systems may be involved. To identify genes induced in the bovine endometrium by the signaling of the embryo, a combination of subtracted cDNA libraries and cDNA array hybridization was applied. Monozygotic twin pairs (n = 5) were used as the biological model. Pregnancy was created in one twin by transferring two in vitro-produced embryos on Day 7 of the estrous cycle; the other twin received a sham embryo transfer. Pregnant and nonpregnant twins were slaughtered at Day 18; endometrial tissue samples were recovered and processed for transcriptome analysis as described (Bauersachs et al. 2005 J. Mol. Endocrinol. 34, 889-908). Screening of 4608 clones of two subtracted libraries revealed 90 different up-regulated genes and mRNAs, of which almost 50% are known to be stimulated by type I interferons. Among these interferon-stimulated genes, the ISG15 system is assumed to be of particular interest, and several components were studied in more detail using in situ hybridization. The pattern of mRNA expression suggests that modification of endometrial proteins through ISG15ylation plays a fundamental role during the pre-implantation period. A classification of the identified genes based on Gene Ontologies revealed the prevalence of genes involved in regulation of gene expression, cell communication, cell growth, cell differentiation, cell proliferation, and cell adhesion, and also the prevalence of genes with immune-related functions. These results underline the intense response of the endometrium to the presence of a conceptus, culminating in the preparation of the maternal environment for embryonic implantation. Further, for eleven selected genes the expression in the endometrium was quantified by the use of real-time RT-PCR. Overall, the results of quantitative RT-PCR and array hybridization correlated very well. To our knowledge this study provides the first holistic gene expression analysis of the bovine endometrium during the pre-implantation period. The results underline the importance of IFN� as an embryo-derived pregnancy recognition signal and depict the molecular mechanisms at the mRNA level underlying the intense embryo-maternal dialog taking place at Day 18 of gestation.

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Epidermal growth factor receptor and ligands in elongating bovine blastocysts

Cited by 36 publications

References 48 publications

Expression of proto-oncogenes in bovine preimplantation blastocysts

Expression of proto-oncogenes in bovine preimplantation blastocysts

Blastocyst elongation, trophoblastic differentiation, and embryonic pattern formation

2 Identification of Genes Induced by the Conceptus in the Bovine Endometrium During the Pre-Implantation Period

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