Submitted June 25, 2004
Returned for revision July 20, 2004
Accepted August 27, 2004
Pregnancy
Reduced Collagen and Ascorbic Acid Concentrations and
Increased Proteolytic Susceptibility with Prelabor Fetal Membrane Rupture in Women
Emma L Stuart ,
Gareth S Evans ,
Yu Shan Lin ,
and
Hilary J Powers *
* To whom correspondence should be addressed. E-mail: h.j.powers{at}sheffield.ac.uk.
Abstract
Prelabour rupture of the fetal membranes affects approximately 10% of women at term resulting in an increased risk of maternal and neonatal infection. Evidence suggests that membrane rupture is related to biochemical processes involving the extracellular matrix of the membranes. We tested the hypothesis that prelabour ruptured membranes are characterised by reduced collagen concentrations, altered collagen crosslink profiles and increased concentrations of biomarkers of oxidative damage. We also set out to determine whether these effects are modulated by ascorbic acid status. In a case-control study we explored the role that ascorbic acid, oxidative stress, collagen and collagen crosslinks play in determining membrane integrity and developed a functional assay to assess membrane proteolytic susceptibility. Prelabour ruptured membrane had a reduced ascorbic acid concentration in comparison with controls whilst protein carbonyl and malondialdehyde concentrations were increased. Collagen concentrations were also reduced in prelabour ruptured membrane, and whilst the concentration of collagen crosslinks was not significantly different between prelabour and timely ruptured membrane there was a regional variation in crosslink ratio within the amniotic sac. Proteolytic resistance in vitro was reduced in prelabour ruptured membrane and also exhibited regional variation within the amniotic sac. Our findings are strongly supportive of a role for the enhanced degradation of membrane collagen in the determination of prelabour rupture of fetal membranes. The formation of the rupture initiation site is a function of a regional variation in collagen crosslink ratio. Tissue ascorbic acid status may be an important mediator of these processes.
Key words:
Pregnancy •
Conceptus
