Matrix metalloproteinases-2 and-9 and their endogenous tissue inhibitors in fetal membrane repair following fetoscopy in a rabbit model

The cellular mechanisms underlying fetal membrane repair are poorly underst ood. Matrix metalloproteinases (MMP) and the endogenous tissue inhibitors o f metalloproteinases (TIMP) play a key role in the control of turnover of e xtracellular matrix in fetal membranes at normal parturition and preterm pr elabour rupture of the fetal membranes (PPROM), The time course of secretio n of MMP-5 (72 kDa, gelatinase A) and MMP-9 (92 kDa, gelatinase B) and TIMP into extra-embryonic coelomic, allantoic and amniotic fluids in a rabbit m odel was examined. Furthermore, to evaluate their role in fetal membrane re pair, the changes induced by fetoscopy at mid-gestation (23 days; gestation length is 32 days) were investigated. Zymography showed predominantly secr etion of latent MMP-2 at 18, 23 and 30 days of gestation in all gestational compartments. Reverse zymography detected a broad range of TIMP activity w ith molecular weights of 27-30 kDa (TIMP-1, glycosylated TIMP-3 and TIMP-4) , 24 kDa (unglycosylated TIMP-3) and 21 kDa (TIMP-5). Following fetoscopy, both MMP-2 and TIMP increased significantly in amniotic fluid and extra-emb ryonic coelomic fluid, but not in allantoic fluid, as demonstrated by densi tometric analyses. These findings indicate a modulating role for MMP and TI MP in the repair processes following a surgically induced fetal membrane de fect.