Expression of the angiogenic growth factors VEGF, FGF-2, EGF and their receptors in normal human endometrium during the menstrual cycle.
Angiogenesis is an important but poorly understood process of the cycling endometrium. Endometrial angiogenesis is believed to be regulated by angiogenic growth factors under the influence of ovarian steroids. Vascular endothelial growth factor (VEGF) and its receptors VEGFR-1 and VEGFR-2, fibroblast growth factor 2 (FGF-2) and its receptors FGFR-1 and FGFR-2, as well as epidermal growth factor (EGF) and its receptor EGFR are believed to be important in the control of angiogenesis in the human endometrium. Their expression was examined by immunohistochemistry in endometrial biopsies obtained from 16 healthy women with proven fertility. Western blot analysis showed that the primary antibodies used were specific for their epitopes. We found that VEGF, FGF-2, EGF and their receptors were all expressed, especially in and/or around blood vessels, thus supporting the hypothesis that these peptides contribute to the regulation of angiogenesis and blood vessel function in the human endometrium. The receptors VEGFR-1, VEGFR-2, FGFR-2 and EGFR were co-expressed and exhibited their strongest expression during the beginning of the secretory phase, coinciding with the developing endometrial oedema and formation of a complex subepithelial capillary plexus. No correlation was seen between receptor expression and stromal blood vessel density.
Möller
B
B
Department of Women's and Children's Health, Section for Obstetrics and Gynaecology, Uppsala University, SE-751 85 Uppsala, Sweden.
Rasmussen
C
C
Lindblom
B
B
Olovsson
M
M
D000328:Adult; D015153:Blotting, Western; D004717:Endometrium / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D016228:Endothelial Growth Factors / Q000096:biosynthesis*; D004815:Epidermal Growth Factor / Q000096:biosynthesis*; D066246:ErbB Receptors / Q000096:biosynthesis*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis*; D006801:Humans; D007124:Immunoenzyme Techniques; D008222:Lymphokines / Q000096:biosynthesis*; D008597:Menstrual Cycle / Q000502:physiology*; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis*; D017978:Receptors, Growth Factor / Q000096:biosynthesis*; D040262:Receptors, Vascular Endothelial Growth Factor; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D017468:Receptors, Fibroblast Growth Factor; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; C496348:FGFR1 protein, human; C496353:FGFR2 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1