Proinflammatory Cytokines Found in Amniotic Fluid Induce Collagen Remodeling, Apoptosis, and Biophysical Weakening of Cultured Human Fetal Membranes1

The mechanisms by which fetal membranes (FM) rupture during the birth process are unknown.We have recently reported that FM weaken, at least in part, because of a developmental process of extracellular matrix remodeling and apoptosis. We now hypothesize that cytokines that normally increase in amniotic fluid at term induce FM collagen remodeling and apoptosis with concomitant weakening. Full-thickness FM frag-ments were cultured with (0–100ng/ml) or without tumor necrosis factor (TNF) or interleukin 1, beta (IL1B). Physical properties were then examined with specially adapted industrial rupture strength testing equipment. Cultured FM were also evaluated for evidence of collagen remodeling and apoptosis. Cytokine-treated FM exhibited a dose-dependent decrease in strength and work to rupture. Compared with controls, th