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Menstrual activity of matrix metalloproteinases is decreased in endometrium regenerating after thermal ablation
J L Brun1, C Galant, D Delvaux
1Department of Gynaecology and Obstetrics, Hôpital Universitaire Pellegrin, Place Amélie-Raba-Léon, F-33076 Bordeaux, France. jean-luc.brun@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.
Insights
Increased tissue inhibitors of matrix metalloproteinases (TIMPs) in the endometrium after thermal ablation reduce extracellular matrix degradation, leading to less menstrual bleeding.
Area of Science:
- Reproductive biology
- Gynecology
- Biochemistry
Background:
- Menstruation involves increased matrix metalloproteinase (MMP) activity.
- The correlation between MMP activity and menstrual bleeding volume is not well understood.
Purpose of the Study:
- To investigate the relationship between MMPs, tissue inhibitors of MMPs (TIMPs), and extracellular matrix (ECM) degradation during menstruation.
- To understand the molecular mechanisms behind reduced menstrual bleeding after endometrial thermal ablation.
Main Methods:
- Histochemistry to assess ECM degradation.
- Immunohistochemical labeling and zymographic analysis for MMP-2, MMP-9, and TIMP-1, -2, -3 expression and activity.
- Endometrial tissue samples from women with menorrhagia and after thermal ablation treatment.
Main Results:
- Regenerated endometria post-ablation showed reduced collagen lysis and increased TIMP-1 and TIMP-2.
- Treated endometria had more latent MMP-2 but less active MMP-9 compared to untreated menorrhagic endometria.
Conclusions:
- Increased TIMP expression in regenerated endometria after thermal ablation reduces ECM degradation.
- This study provides a molecular explanation for decreased menstrual bleeding following endometrial ablation.
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