The role of hyaluronic acid as a mediator and regulator of cervical ripening

During pregnancy, hyaluronic acid (HA) concentration in the human cervix isvery low, but increases rapidly at the onset of labour. HA has a highaffinity for water molecules and hence can maintain tissue hydration. HAcan stimulate collagenase production in rabbit cervix, and also stimulatesmigration and function of polymorphonuclear leukocytes in the tissues. Itis an endogenous regulator of interleukin- 1 (IL-1). We hypothesized thatHA plays an essential role during cervical ripening. The effect ofexogenous application of HA (20 mg) on non-pregnant and pregnant (day 23)rabbit cervices was compared with controls. HA induced cervical ripening inboth pregnant and non- pregnant animals, and cervical water content wassignificantly increased. Tissue collagen was markedly decreased. Thelocalization and distribution of HA and HA receptor CD44 was determined innon-pregnant and pregnant human cervical connective tissue usingbiotinylated HA binding protein and CD44 monoclonal antibodies. Both werewidely distributed in the connective tissues, especially around the bloodvessels and cervical glands. The effect of IL-8 (50, 100, 150 and 200ng/ml) on HA production and hyaluronidase (HAase) activity was investigatedin cultures of lower uterine segment collected during elective Caesareansections. HA production was stimulated in a dose- dependent manner; therewas no effect on hyaluronidase activity. HA administration (0.5, 1 and 2mg/ml) stimulated the activities of collagenase and gelatinase togetherwith IL-8 production in the culture supernatants. Thus HA may play animportant role in cervical ripening, being involved in the regulation ofcervical tissue water content, collagenolytic enzymes and cytokines.