Abstract
Cervical ripening is a cytokine-triggered process with substantial remodelling of the cervical extracellular matrix. Interleukin-8 (IL-8) is an important cytokine in cervical maturation. Glycosaminoglycans are also included in this process, but their role in not clearly understood. The effects of heparan sulphate (HS), hyaluronic acid (HA), IL-8, HS + IL-8 and HA + IL-8 on biochemical properties of the cervix were examined in non-pregnant rabbits. The changes in vascular pattern with collagen structure of the cervices and immunohistochemical studies, together with the relative collagen concentrations, were determined. A reduction in relative collagen concentration was significant after HS + IL-8, IL-8 and HA + IL-8 treatment (all P < 0.0001). Gel electrophoresis analysis showed that IL-8 bound preferentially to HS than to HA. Neutrophils were significantly increased in number (P < 0.0001) and located predominantly beneath the glandular epithelium and around the blood vessels after HS + IL-8 treatment. HS + IL-8 treatment caused cervices to increase their water content and become oedematous. The collagen fibres were considerably dissociated, the interfibrillar spaces markedly dilated, and the blood vessels notably increased and dilated. We conclude that binding to HS enhances the activity of IL-8 in inducing cervical maturation.
Highlights
The non-pregnant cervix is a fibrous structure which undergoes modifications during pregnancy to allow sufficient softening and growth for the passage of the fetus at birth (Harkness and Harkness, 1959; Friedman, 1980; Calder, 1981; Fitzpatrick, 1981)
This study demonstrated that the binding of IL-8 to heparan sulphate (HS) enhances its activity in cervical connective tissue in rabbits
The most striking finding of the present study was that the changes in biochemical components in the cervix of rabbits were markedly influenced by HS ϩ IL-8
Summary
The non-pregnant cervix is a fibrous structure which undergoes modifications during pregnancy to allow sufficient softening and growth for the passage of the fetus at birth (Harkness and Harkness, 1959; Friedman, 1980; Calder, 1981; Fitzpatrick, 1981). It is well established that the transformation of the uterine cervix to a soft and compliant structure during pregnancy is crucial for a normal delivery. This ripening process can be explained mainly in terms of connective tissue biology (Huszar and Walsh, 1991). A marked increase in the GAG content of the cervix during late pregnancy has been demonstrated in rats, rabbits, sheep and humans
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