Dehydroepiandrosterone sulphate promotes hyaluronic acid-induced cervical ripening in rabbits

Hyaluronic acid (HA) stimulates the synthesis of interleukin (IL) 8, while dehydroepiandrosterone sulphate (DHEA-S) induces the expression of IL-8 and its receptor in the human cervical fibroblast. This has led us to investigate the effect of DHEA-S on HA-induced cervical ripening. Experiments were performed in pregnant rabbits using vaginal suppositories containing 1 mg HA, 30 mg DHEA-S, 30 mg DHEA-S + 0.1 mg HA, 30 mg DHEA-S + 1 mg HA, and 500 mu l Witepsol-50 base (control). The effects were evaluated by measuring collagenase, gelatinase and elastase activities, water content, neutrophil infiltration, relative collagen concentration and histological assessment. The activities of collagenase, gelatinase and elastase were significantly increased in rabbits treated with DHEA-S + 1 mg HA compared with rabbits treated with DHEA-S + 0.1 mg HA (P < 0.009, P < 0.001, P < 0.009 respectively). Water content was markedly increased in rabbits treated with DHEA-S + 1 mg HA compared with DHEA-S + 0.1 mg HA treatment (P < 0.05). Neutrophil infiltration was markedly increased, while relative collagen concentration was significantly decreased with DHEA-S + 1 mg HA compared with the DHEA-S + 0.1 mg HA approach (P < 0.001, P < 0.002). The histology of cervices treated with DHEA-S + 1 mg HA showed the density of collagen to be markedly decreased, and collagen fibres irregularly separated. Increased vascularity with massive dilatation of blood vessels was also observed in these rabbits. We conclude that DHEA-S upregulates the HA-induced cervical ripening process.