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BOR - Papers in Press, published online ahead of print September 8, 2004.
Biol Reprod 2004, 10.1095/biolreprod.104.033381
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BIOLOGY OF REPRODUCTION 72, 230–235 (2005)
DOI: 10.1095/biolreprod.104.033381
© 2005 by the Society for the Study of Reproduction, Inc.

Reduced Collagen and Ascorbic Acid Concentrations and Increased Proteolytic Susceptibility with Prelabor Fetal Membrane Rupture in Women1

Emma L. Stuart3, Gareth S. Evans4, Yu Shan Lin3, and Hilary J. Powers2,3

Human Nutrition Unit,3 University of Sheffield, Sheffield S5 7AU, United Kingdom Academic Unit of Child Health,4 University of Sheffield, Sheffield S10 2TH, United Kingdom

Prelabor 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 prelabor ruptured membranes are characterized by reduced collagen concentrations, altered collagen cross-link 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 cross-links play in determining membrane integrity and developed a functional assay to assess membrane proteolytic susceptibility. Prelabor ruptured membrane had a reduced ascorbic acid concentration in comparison with controls while protein carbonyl and malondialdehyde concentrations were increased. Collagen concentrations were also reduced in prelabor ruptured membrane, and while the concentration of collagen cross-links was not significantly different between prelabor and timely ruptured membrane, there was a regional variation in cross-link ratio within the amniotic sac. Proteolytic resistance in vitro was reduced in prelabor 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 prelabor rupture of fetal membranes. The formation of the rupture initiation site is a function of a regional variation in collagen cross-link ratio. Tissue ascorbic acid status may be an important mediator of these processes.

1 The Nutricia Research Foundation provided funding support; this sponsor had no role in study design, data collection, data analysis, data interpretation, or writing and submission of this report.

2 Correspondence: Hilary Powers, Human Nutrition Unit, University of Sheffield, Coleridge House, Northern General Hospital, Herries Road, Sheffield S5 7AU, UK. FAX: 44 011 4261 0112; h.j.powers{at}sheffield.ac.uk






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Copyright © 2005 by the Society for the Study of Reproduction.