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Matrix metalloproteinases and their tissue inhibitors in preterm perinatal complications
Julia V Cockle1, Nadia Gopichandran, James J Walker
1Perinatal Research Group, Leeds, United Kingdom.
Abstract:
The objective of this article is to review the role of matrix metalloproteinases (MMPs) in fetomaternal/neonatal complications of preterm birth. The function of MMPs as proteolytic enzymes involved in tissue remodeling/destruction is reviewed in preterm labor, preeclampsia, premature rupture of membranes, intrauterine growth restriction, chronic lung disease, necrotizing enterocolitis, intraventricular hemorrhage, cystic periventricular leukomalacia, and retinopathy of prematurity. Cytokines, steroid hormones, and reactive oxygen species all regulate MMP labor and expression/activity. In labor, activation follows an inflammatory response, which results in fetal membrane rupture and cervical dilation/ripening, particularly when premature. Expression/activation is elevated during parturition, particularly when premature. While fetal membrane rupture is preceded by increases in tissue-specific MMPs, neonatal complications also ensue from an imbalance between MMPs and their tissue inhibitors. These e fects implicate environmental triggers and a genetic predisposition. MMPs are involved in the perinatal complications of prematurity and are potential targets for therapeutic intervention. Functional MMP genetic polymorphisms may assist in identifying patients at risk of complications.
Insights
Matrix metalloproteinases (MMPs) play a crucial role in preterm birth complications. Understanding MMPs and their inhibitors could lead to new therapies for preventing adverse perinatal outcomes.
Area of Science:
- Biochemistry
- Reproductive Biology
- Neonatal Medicine
Background:
- Preterm birth is a leading cause of neonatal mortality and morbidity.
- Matrix metalloproteinases (MMPs) are enzymes involved in tissue remodeling and destruction.
- Their dysregulation is implicated in various pregnancy and neonatal complications.
Purpose of the Study:
- To review the role of MMPs in fetomaternal and neonatal complications associated with preterm birth.
- To explore the regulation of MMPs by cytokines, hormones, and oxidative stress.
- To identify MMPs as potential therapeutic targets for preterm birth complications.
Main Methods:
- Literature review of studies on MMPs in preterm labor, preeclampsia, premature rupture of membranes, and neonatal outcomes.
- Analysis of MMP involvement in tissue remodeling and destruction processes.
- Examination of regulatory factors influencing MMP expression and activity.
Main Results:
- MMP activation is linked to inflammatory responses in preterm labor, leading to membrane rupture and cervical changes.
- Elevated MMP expression/activation occurs during premature parturition.
- An imbalance between MMPs and their inhibitors contributes to neonatal complications like chronic lung disease and necrotizing enterocolitis.
- MMPs are implicated in intraventricular hemorrhage, cystic periventricular leukomalacia, and retinopathy of prematurity.
Conclusions:
- MMPs are significantly involved in the pathophysiology of preterm birth and its associated perinatal complications.
- Therapeutic interventions targeting MMPs may offer a novel approach to managing these conditions.
- Genetic polymorphisms in MMPs could serve as biomarkers for identifying at-risk individuals.
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