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Hum. Reprod. Advance Access originally published online on December 1, 2008
Human Reproduction 2009 24(2):333-340; doi:10.1093/humrep/den392
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Menstrual activity of matrix metalloproteinases is decreased in endometrium regenerating after thermal ablation

J.L. Brun1,4,{dagger}, C. Galant2,3,{dagger}, D. Delvaux2, P. Lemoine2, P. Henriet2, P.J. Courtoy2 and E. Marbaix2,3

1 Department of Gynaecology and Obstetrics, Hôpital Universitaire Pellegrin, Place Amélie-Raba-Léon, F-33076 Bordeaux, France 2 Cell Biology Unit, de Duve lnstitute, Brussels, Belgium 3 Department of Pathology, Saint-Luc University Clinics, Université catholique de Louvain, Avenue Hippocrate 10, B-1200 Bruxelles, Belgium

4 Correspondence address. E-mail:jean-luc.brun{at}chu-bordeaux.fr

BACKGROUND: Menstruation is associated with a striking increase in matrix metalloproteinase (MMP) activity. However, it is still unknown whether the level of MMP activity correlates with the amount of menstrual bleeding.

METHODS: We used histochemistry to investigate the degradation of the extracellular matrix (ECM), and immunohistochemical labelling and zymographic analysis to determine the level of expression and activity of MMP-2 and -9, and of their tissue inhibitors (TIMPs) -1, -2 and -3, in endometria sampled during menstruation in 14 women experiencing excessive menstrual bleeding and in 10 women successfully treated for menorrhagia by thermal ablation of the endometrium.

RESULTS: After thermal ablation, regenerated menstrual endometria showed reduced areas of collagen fibre lysis and increased content of TIMP-1 and TIMP-2 compared with endometria from non-treated menorrhagic women. Surprisingly, treated endometria contained more latent gelatinase A (proMMP-2) but a lower proportion of the active form of gelatinase B (MMP-9) than non-treated endometria.

CONCLUSIONS: These results suggest that ECM degradation is decreased at menstruation in the endometrium regenerated after thermal ablation, mostly because of an increased TIMP expression. This represents the first molecular explanation for the decreased amount of menstrual bleeding.

Key words: MMP/endometrial ablation/menstruation

{dagger} Both authors contributed equally to the study

Submitted on July 5, 2008; resubmitted on September 29, 2008; accepted on October 8, 2008.


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