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SummaryChronic degenerative changes to the endometrium include endometrial fibrosis, involving a deposition of fibrous tissue in the endometrial stroma and around the endometrial glands. In this study it is hypothesised that endometrial fibrosis is a result of extracellular matrix (ECM) remodelling following endometritis involving MMP-9 and -2 and the tissue inhibitors of MMPs (TIMPs). Endometrial biopsies and low volume uterine flushes were collected from five mares at oestrus and dioestrus before inducing endometritis. Endometritis was induced by introducing Streptococcus zooepidemicus into the uterus in oestrus and dioestrus, and by breeding the mares in oestrus. Gelatin zymography on uterine lavage fluid revealed that basal activities of MMP-2 and MMP-9 did not differ significantly between oestrus and dioestrus. A significant increase (p<0.05) in MMP-9 and -2 activities was detected post-inoculation in oestrus and dioestrus, and post-breeding in oestrus when compared to controls. In situ zymography demonstrated MMP-9 activity in eosinophils in endometrial biopsies. Basal activity of TIMP-2 was significantly higher (p<0.05) during dioestrus than during oestrus, and activity decreased during induced endometritis. The study showed that MMP-9 and MMP-2 are likely to play a role in the repair processes following endometritis and that MMP-9 is secreted by eosinophils in the endometrial stroma. Furthermore, the inhibitory activity of TIMP-2 is decreased during endometritis, in concert with the increased activity of MMP-9 and -2.Keywords: Mare, endometritis, fibrosis, matrix metalloproteinases, TIMPs, reproduction Aktivität der Matrix Metalloproteinasen MMP-9 und MMP-2 in Uterusspülproben im Verlauf einer induzierten equinen EndometritisDie endometriale Fibrose, eine chronisch-degenerative Veränderungen des Endometriums, ist durch eine Einlagerung von fibrösem Gewebe sowohl in das endometriale Stroma als auch um die endometrialen Drüsen gekennzeichnet. In der vorliegenden Studie wird angenommen, dass die endometriale Fibrose das Ergebnis eines durch die Endometritis ausgelösten Umbaus der extrazellulären Matrix ist, an welchem MMP-9 und MMP-2 sowie deren Inhibitoren (TIMPs) beteiligt sind. Als Kontrolle dienten im Östrus und Diöstrus entnommene Endometriumbiopsien und kleinvolumigen Uterusspülproben von 5 Stuten vor Endometritisinduzierung. Anschließend wurde eine Endometritis mittels intrauteriner Verabreichung von Streptococcus zooepidemicus zum Zeitpunkt des Östrus und des Diöstrus beziehungsweise durch eine Belegung im Östrus induziert. Mit Hilfe einer Gelatin-Zymographie konnten in den uterinen Spülproben keine signifikanten Unterschiede hinsichtlich der Grundaktivität von MMP-2 und MMP-9 zwischen Östrus und Diöstrus nachgewiesen werden. Im Vergleich zu den Kontrollproben konnte jedoch sowohl postinfektiös im Östrus und Diöstrus als auch nach der Belegung im Östrus ein signifikanter Anstieg (p<0,05) der Aktivität von MMP-2 und MMP-9 beobachtet werden. Zudem zeigte die in situ Zymographie eine Aktivität von MMP-...

The process of parturition involves a sequence of events that require extensive tissue remodelling. These events include foetal membrane rupture, placental detachment and post-partum involution of the uterus. Normally, foaling in the mare is a quick and dynamic process. Precisely orchestrated tissue remodelling mechanisms are required to control these fast events, hereunder the rupture of the foetal membranes and detachment of the placenta. In tissue remodelling, the matrix metalloproteinases (MMPs) are a much-studied family of enzymes that are involved in extracellular matrix (ECM) degradation. In the mare, invasive chorionic girdle cells have been found to produce MMP-2 and MMP-9, a likely event in the establishment of endometrial cup tissue [1]. The levels of MMP-9 in human and rodent foetal membranes and fluids increased markedly with the onset of labour, relating this enzyme with the rupture of foetal membranes and detachment from the uterus [2]. It is not known whether MMP activity is increased in late gestation or at parturition in mares. The aim of this study was to illustrate the secretion and localisation of MMP-9 and -2 in equine amniotic fluid during late pregnancy and foaling.A longitudinal study was used to determine the activities of MMP-9 and MMP-2 in equine amniotic fluid through gestation and during foaling in pony mares. The concentrations of MMP-9, MMP-2 and TIMP-2 in amniotic fluid were normally distributed and therefore parametric tests were used: Student's t-test to compare between gestational ages and outcome of pregnancy (normal birth, stillbirth or abortion), and the activities during the last 3 days before foaling and during foaling.All zymograms detected MMP-9 and MMP-2, and no significant changes were detected in mid gestation. Approaching normal foaling MMP-9 was present in increasing amounts. Activity of MMP-2 was detected in varying amounts in all samples, but there was no significant change in values through the sampling period. In the days before stillbirth and abortion there was no significant difference in activities of MMP-9 or -2.When values in the last 3 days before normal birth were compared with values during foaling, activities of MMP-9 and MMP-2 were significantly reduced during foaling. Activities of MMP-9 and MMP-2 in the last 3 days before stillbirth or abortion were also significantly higher than during foaling.This study shows that MMP-9 production is induced under specific conditions around normal parturition, and that MMP-2 seems to be constitutively expressed at an unchanging level throughout the last days of gestation. Also, MMP-9 activity is highest in the last three days before foaling and is significantly reduced during foaling.