Wall discontinuities and increased expression of vascular endothelial growth factor-A and vascular endothelial growth factor receptors 1 and 2 in endometrial blood vessels of women with menorrhagia.
OBJECTIVE
To investigate whether the structure or regulation of the growth of endometrial blood vessels might be abnormal in women with idiopathic menorrhagia (IM). Perturbation of angiogenesis is associated with IM.


METHODS
Prospective, clinical study.


METHODS
Department of gynecology at a university hospital.


METHODS
Twenty-four patients with IM, and 18 women with eumenorrhea.


METHODS
Endometrial biopsy samples underwent immunohistochemical staining for CD34, CD31, von Willebrand factor, vascular endothelial growth factor (VEGF)-A, and VEGF receptors 1 and 2.


METHODS
Differences in immunostaining for these markers by computer-assisted stereological analysis.


RESULTS
Endometrial vessels in patients and controls manifested focal discontinuities, or gaps, in endothelial staining for CD34, CD31, and von Willebrand factor. Electron and confocal microscopy revealed that perivascular cells, probably pericytes, covered these gaps in the vessel wall. The relative size of the gaps was significantly greater in patients with IM than in controls. Vessel circumference was also larger, and more vessels were positive for VEGF-A and for VEGF receptors 1 and 2, in patients than in controls. Gap size was significantly correlated with the number of vessels expressing VEGF-A or VEGF receptor 1.


CONCLUSIONS
Endometrial blood vessels possess a discrete morphology that is characterized by endothelial gaps, and these gaps [1] are more pronounced in women with IM, [2] are related to overexpression of VEGF-A and VEGF receptor 1, and [3] might contribute to IM, e.g., by destablizing vessels.
Mints
Miriam
M
Division of Obstetrics and Gynecology, Department of Clinical Science, Karolinska Institutet and Karolinska University Hospital Huddinge, Stockholm, Sweden. miriam.mints@telia.com <miriam.mints@telia.com>
Hultenby
Kjell
K
Zetterberg
Eva
E
Blomgren
Bo
B
Falconer
Christian
C
Rogers
Rick
R
Palmblad
Jan
J
D001808:Blood Vessels / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D004715:Endometriosis / Q000235:genetics* / Q000473:pathology; D004717:Endometrium / Q000098:blood supply* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008595:Menorrhagia / Q000235:genetics* / Q000473:pathology; D008854:Microscopy, Electron; D011446:Prospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*
D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2