Matrix metalloproteinases in the cervical mucus plug in relation to gestational age, plug compartment, and preterm labor

Naja Becher,Niels Uldbjerg,Carl C Danielsen,Merete Hein

doi:10.1186/1477-7827-8-113

Naja Becher, Niels Uldbjerg + Show 2 more

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https://doi.org/10.1186/1477-7827-8-113

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Abstract

BackgroundHigh concentrations of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been identified in the cervical mucus plug (CMP) at term of pregnancy. Their physiological and pathophysiological implications, however, remain to be elucidated, and CMPs from preterm labor have never been examined. This study was therefore conducted to describe the concentrations of MMP-2, TIMP-1, MMP-8 and MMP-9 in the CMP in relation to gestational age, IL-8 as an indicator of inflammation, compartment of the CMP, and preterm labor.MethodsAn aliquot of the distal plug compartment facing the vaginal microflora (CMP-dist) was collected from non-pregnant (n = 15), early pregnant (n = 15) and term pregnant women (n = 15). Whole CMPs shed during active vaginal term (n = 15) and preterm (n = 4) labor were also included. Protein concentrations were determined by enzyme-linked immunosorbent assay (ELISA).ResultsMMP-2 was not detectable in the non-pregnant CMP-dists whereas high concentrations were found in early pregnancy followed by an 85% decline at term. High concentrations of TIMP-1 were found in both the non-pregnant and early pregnant CMP-dists with a 90% decline at term. Consequently, the molar TIMP/MMP ratio was 40 in the non-pregnant state and 0.2 at term. The MMP-2 and TIMP-1 concentrations were alike in the CMP-dists and the whole CMPs.MMP-8, MMP-9, and IL-8 were mainly found in the distal CMP compartment. MMP-8 and MMP-9 concentrations were several fold increased in this compartment during pregnancy compared to the non-pregnant state. In the preterm whole CMPs, MMP-8, MMP-9 and IL-8 were 2 to 5 fold increased compared to term whole CMPs.ConclusionsThese results suggest that CMP MMP-2 reflects the non-leukocyte dependent cervical remodeling that occurs in early pregnancy, whereas MMP-8 and MMP-9 are involved in the defense against ascending infections primarily located to the distal compartment of the CMP. The upregulation of MMP-8, MMP-9 and IL-8 in whole CMPs from preterm labor may indicate the involvement of an intrauterine infection.

Highlights

High concentrations of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been identified in the cervical mucus plug (CMP) at term of pregnancy
We do not know whether CMP MMPs reflect MMP activity in the cervical stroma and in the fetal membranes, or whether they are involved in processes within the CMP, e.g. local inflammatory processes
The mean TIMP-1 concentration in the early pregnant CMP-dists was unchanged from that found in the nonpregnant CMP-dists (P = 0.2) and followed by a decline at term (P < 0.001) when using post hoc pairwise comparison (Figure 2B)

Summary

Introduction

High concentrations of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been identified in the cervical mucus plug (CMP) at term of pregnancy. Their physiological and pathophysiological implications, remain to be elucidated, and CMPs from preterm labor have never been examined. The cervical mucus plug (CMP) provides a protective barrier against ascending infection by possessing strong antibacterial properties and significant innate and Matrix metalloproteinases (MMPs) are proteolytic enzymes with the potential to degrade extracellular matrix components [8] and to activate cytokines and anti-microbial peptides [9]. We do not know whether CMP MMPs reflect MMP activity in the cervical stroma and in the fetal membranes, or whether they are involved in processes within the CMP, e.g. local inflammatory processes

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