MMP/TIMP imbalance in amniotic fluid during PROM: an indirect support for endogenous pathway to membrane rupture

Abstract

Active, TIMP free forms of MMP2 and 9 are increased in the amniotic fluid of women with PROM. These MMPs can degrade the amniochorion basement membranes and other ECM components resulting in PROM.

Matrix metalloproteinases-2, -3 and tissue inhibitors of metalloproteinases-1, -2 in placentas from preterm pregnancies and their association with one-carbon metabolites

“…Fortunato et al (1999a) have reported increased MMP2 levels in the amniotic fluid of women with PPROM, suggesting that MMP2 is implicated in the mechanism responsible for rupture of membranes. In contrast, other reports suggest no changes in amniotic fluid MMP2 levels in women with spontaneous labor (term and preterm) and rupture of membranes (term and preterm) (Maymon et al 2000c(Maymon et al , 2001).…”

“…All the four TIMPs inhibit MMPs but differ in their affinities for different inhibitor-protease pairs (Brew & Nagase 2010). A number of studies have examined the levels of TIMP1 and TIMP2 in the amniotic fluid and fetal membranes both in term and preterm pregnancy (Athayde et al 1999, Fortunato et al 1999a, Maymon et al 2001, Goldman et al 2003. However, the results are inconsistent.…”

“…However, the results are inconsistent. Fortunato et al (1999a) have shown elevated amniotic fluid TIMP1 levels in women with PROM, while studies have reported that TIMP1 levels decrease before labor (Makrakis et al 2003) and following PPROM (Nishihara et al 2008). Further, it is suggested that spontaneous labor (term and preterm) and infection are associated with significant decreased concentrations of TIMP2 (Maymon et al 2001).…”

Weakening and Rupture of Human Fetal Membranes – Biochemistry and Biomechanics

“…MMP-1 predominates prior to the onset of contractions as described by Bryant-Greenwood and Yamamoto. FM MMP-2 is constitutive and reportedly does not respond to cytokines or change with PPROM or labor (term or preterm) [Fortunato et al, 1999;Maymon et al, 2001;Xu et al, 2002]. In contrast, both active and latent forms of Bryant-Greenwood et al, 1995;Osmers et al, 1995;Athayde et al, 1999;Vadillo-Ortega et al, 2002).…”

The MMP-9/TIMP-1 imbalance and the reduced level of TGF-β in the cervical area of amniotic membrane is a possible risk factor of PROM and premature labor — proof-of-concept study

“…It was also lower than in corresponding area of membranes [20,21]. Another group reported elevated TIMP-1 levels in amniotic fluid samples derived from deliveries complicated with PROM, nevertheless this study did not include MMP-9 assessment or MMP-9/TIMP-1 ratio [22].…”