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

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. 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. 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. 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.