Differential expression of the receptor tyrosine kinase EphB4 and its ligand Ephrin-B2 during human placental development

Chennakesava, C S; Di Santo, S; Ziemiecki, A; Schneider, H; Andres, A-C (2006). Differential expression of the receptor tyrosine kinase EphB4 and its ligand Ephrin-B2 during human placental development. Placenta, 27(9-10), pp. 959-67. Amsterdam: Elsevier 10.1016/j.placenta.2005.10.008

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Normal placentation involves the development of an utero-placental circulation following the migration of the extravillous cytotrophoblasts into the decidua and invasion of the spiral arteries, which are thereby transformed into large vessels of low resistance. Given the documented role of the receptor tyrosine kinase EphB4 and its ligand ephrin-B2 in the establishment of the embryonal vascular network, we hypothesized that these molecules are also instrumental in the development of the human placenta. Monitoring the expression during placental development revealed that in first trimester and term placentae both molecules are equally expressed at the RNA level. In contrast, the protein levels were significantly reduced during gestation. Immunohistochemistry revealed a distinct localization of the EphB4 and ephrin-B2 proteins. EphB4 was predominantly expressed in the villous syncytial trophoblast layer and in a subset of intravillous capillaries. Prominent expression was also observed in the extravillous cytotrophoblast giant cells. In contrast, ephrin-B2 expression was detected in the villous cytotrophoblast and syncytial trophoblast cell layers, as well as initially in all intravillous capillaries. Strong expression was also observed in extravillous anchoring cytotrophoblast cells. Hypoxia is a major inducer of placental development. In vitro studies employing trophoblast-derived cell lines revealed that predominantly ephrin-B2 expression is induced by hypoxia, however, in an Hif-1alpha independent manner. These experiments suggest that EphB4 and ephrin-B2 are instrumental in the establishment of a functional placental structure and of the utero-placental circulation.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Unit Tiefenau Hospital (discontinued) > Forschungsgruppe Biologie und Karzinogenese der Brustdrüse (discontinued)
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Gynaecology

UniBE Contributor:

Ziemiecki, Andrew; Schneider, Henning and Andres, Anne Catherine

ISSN:

0143-4004

ISBN:

16343615

Publisher:

Elsevier

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:48

Last Modified:

28 Jan 2019 14:46

Publisher DOI:

10.1016/j.placenta.2005.10.008

PubMed ID:

16343615

Web of Science ID:

000240312200004

URI:

https://boris.unibe.ch/id/eprint/19907 (FactScience: 2984)

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