Reduced levels of VEGF-A and MMP-2 and MMP-9 activity and increased TNF-alpha in menstrual endometrium and effluent in women with menorrhagia.
BACKGROUND
Heavy regular menstrual periods (menorrhagia) are an important cause of ill health in women and remain the leading indication for hysterectomy. Abnormalities of the endometrial blood vessels are among the possible causes of this condition. Many different factors affect endothelial cell growth, function and vessel remodelling. We sought to determine whether the levels of vascular endothelial growth factor-A (VEGF-A), tumour necrosis factor-alpha (TNF-alpha), matrix metalloproteinase (MMP)-2 and MMP-9 and soluble VEGF receptor-1 (VEGF-R1) were altered in the menstrual effluent of women with objective menorrhagia. We have also quantitated the VEGF-A mRNA in the menstruated endometrium.


RESULTS
We recruited 37 women and determined their menstrual blood loss (MBL) over two cycles and collected menstrual effluent during the 2nd day of bleeding for 4 h. There was no difference in the total level of VEGF-A, and neither latent MMP. However, the concentration of VEGF-A was significantly reduced in the women with menorrhagia, as was the VEGF-A mRNA level. In addition, the active forms of both MMPs were markedly reduced and the total sVEGF-R1 as well as the TNF-alpha content were increased.


CONCLUSIONS
This is the first study to show abnormalities of factors important for endothelial cell behaviour in the endometrium of women with menorrhagia. This may underlie the disordered vessel structure and/or function in this condition.
Malik
Shazia
S
Department of Obstetrics and Gynaecology, The Rosie Hospital, Robinson Way, Cambridge, UK. shazymalik@yahoo.co.uk
Day
Kate
K
Perrault
Isabelle
I
Charnock-Jones
D Stephen
DS
Smith
Stephen K
SK
D000328:Adult; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008595:Menorrhagia / Q000378:metabolism*; D008598:Menstruation / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9