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Differential expression of VEGF isoforms and VEGF 164 ‐specific receptor neuropilin‐1 in the mouse uterus suggests a role for VEGF 164 in vascular permeability and angiogenesis during implantation
Author(s) -
Halder J. B.,
Zhao X.,
Soker S.,
Paria B. C.,
Klagsbrun M.,
Das S. K.,
Dey S. K.
Publication year - 2000
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/(sici)1526-968x(200003)26:3<213::aid-gene7>3.0.co;2-m
Subject(s) - angiogenesis , vascular endothelial growth factor , neuropilin 1 , biology , stromal cell , vascular endothelial growth factor a , endocrinology , microbiology and biotechnology , kinase insert domain receptor , medicine , vascular permeability , receptor tyrosine kinase , neuropilin , cancer research , signal transduction , vegf receptors
Summary: The mechanism(s) by which localized vascular permeability and angiogenesis occur at the sites of implantation is not clearly understood. Vascular endothelial growth factor (VEGF) is a key regulator of vasculogenesis during embryogenesis and angiogenesis in adult tissues. VEGF is also a vascular permeability factor. VEGF acts via two tyrosine kinase family receptors: VEGFR1 (Flt‐1) and VEGFR2 (KDR/Flk‐1). Recent evidence suggests that neuropilin‐1 (NRP1), a receptor involved in neuronal cell guidance, is expressed in endothelial cells, binds to VEGF 165 and enhances the binding of VEGF 165 to VEGFR2. We examined the spatiotemporal expression of vegf isoforms, nrp 1 and vegfr 2 as well as their interactions in the periimplantation mouse uterus. We observed that vegf 164 is the predominant isoform in the mouse uterus. vegf 164 mRNA accumulation primarily occurred in epithelial cells on days 1 and 2 of pregnancy. On days 3 and 4, the subepithelial stroma in addition to epithelial cells exhibited accumulation of this mRNA. After the initial attachment reaction on day 5, luminal epithelial and stromal cells immediately surrounding the blastocyst exhibited distinct accumulation of vegf 164 mRNA. On days 6–8, the accumulation of this mRNA occurred in both mesometrial and antimesometrial decidual cells. These results suggest that VEGF 164 is available in mediating vascular changes and angiogenesis in the uterus during implantation and decidualization. This is consistent with coordinate expression of vegfr 2, and nrp 1, a VEGF 164 ‐specific receptor, in uterine endothelial cells. Their expression was low during the first 2 days of pregnancy followed by increases thereafter. With the initiation and progression of implantation (days 5–8), these genes were distinctly expressed in endothelial cells of the decidualizing stroma. Expression was more intense on days 6–8 at the mesometrial pole, the presumptive site of heightened angiogenesis and placentation. However, the expression was absent in the avascular primary decidual zone immediately surrounding the implanting embryo. Crosslinking experiments showed that 125 I‐VEGF 165 binds to both NRP1 and VEGFR2 present in decidual endothelial cells. These results suggest that VEGF 164 , NRP1 and VEGFR2 play a role in VEGF‐induced vascular permeability and angiogenesis in the uterus required for implantation. genesis 26:213–224, 2000. © 2000 Wiley‐Liss, Inc.