Reduced levels of VEGF-A and MMP-2 and MMP-9 activity and increased TNF-α in menstrual endometrium and effluent in women with menorrhagia

Shazia Malik, Kate Day, Isabelle Perrault, D. Stephen Charnock‐Jones, S. K. Smith
In: Human Reproduction · 2006 · vol. 21(8) , pp. 2158–2166 · doi:10.1093/humrep/del089 · PMID:16585124 · W2063006274
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Menorrhagia is associated with reduced VEGF-A and active MMP-2/MMP-9, and increased TNF-α in endometrial effluent and endometrium.

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Abstract

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. METHODS AND 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.

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