title: E-selectin expression and function in a unique placental trophoblast population at the fetal-maternal interface: regulation by a trophoblast-restricted transcriptional mechanism conserved between humans and mice.
abstract: Trophoblast are the earliest differentiated cells to emerge during mammalian ontogeny. Proper differentiation and maturation of trophoblast contributes to the fetal-maternal vascular interface of the mature placenta and is required for all subsequent stages of embryogenesis. Although lineage commitment and early differentiation of trophoblast have been investigated experimentally, molecular markers and regulatory mechanisms operating later in trophoblast development remain uncertain. We now report that E-selectin is expressed in a unique pattern in secondary trophoblast giant cells, trophoblast lining the central artery, and a subpopulation of labyrinthine trophoblast all located at the fetal-maternal interface of the murine placenta. These cells line vascular channels but express a unique profile of gene products not displayed by vascular endothelium. Placentae lacking E-selectin show increased trophoblast glycogen cells and fewer labyrinthine neutrophils compared with normal placentae, suggesting that recognition of E-selectin on trophoblast by counter-receptors on other cells contributes to placental development. Novel, distant first exons direct E-selectin expression in both murine and human placentae, suggesting that evolutionarily conserved and lineage-restricted transcriptional mechanisms regulate expression in homologous trophoblast populations in both species. These results define, at molecular and anatomic levels, a unique population of trophoblast located at the physiologically critical fetal-maternal vascular interface in mice. We also present initial functional characterization of E-selectin in placenta. These results support the general hypothesis that endothelial-leukocyte adhesion molecules performing specialized functions in adults may also function in development of human and murine hemochorial placentae.
authors.affiliation: Vascular Research Division, Department of Pathology, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. milstone@rascal.med.harvard.edu
authors.forename: D S
authors.initials: DS
authors.lastname: Milstone
authors.forename: R W
authors.initials: RW
authors.lastname: Redline
authors.forename: P E
authors.initials: PE
authors.lastname: O'Donnell
authors.forename: V M
authors.initials: VM
authors.lastname: Davis
authors.forename: G
authors.initials: G
authors.lastname: Stavrakis
mesh_terms: D000818:Animals; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002450:Cell Communication; D002454:Cell Differentiation; D019070:Cell Lineage; D019040:E-Selectin / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007150:Immunohistochemistry; D007962:Leukocytes; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000378:metabolism; D010920:Placenta / Q000098:blood supply / Q000166:cytology*; D012333:RNA, Messenger / Q000032:analysis; D017385:Sequence Homology; D014158:Transcription, Genetic; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D019040:E-Selectin; D012333:RNA, Messenger