Preparation of Hyaluronan from Uterine Cervix and Estimation of Its Molecular Weight Uterine cervices

sists mainly of collagen, hyaluronan, and proteoglycan. During gestation, it must close firmly to retain the fetus in the uterus. It undergoes ripening and dilatation at term, forming a parturient canal so that delivery can occur. During ripening, there are increases of collagen degradation in connective tissues, and proteoheparan sulfate, while decorin decreases. Inflammatory mediators, such as interleukin-1 (IL-1) and prostaglandin (PG) E2 are produced, and indeed, the ripening and dilatation of the uterine cervix have been considered as an inflammatory process. It is thought that sex hormones such as progesterone and estrogen play important roles as regulatory factors of these changes in the uterine cervix. Administration of anti-progesterone to pregnant women and to pregnant rats promotes uterine cervical ripening and dilatation. The hyaluronan levels of uterine cervix, cervical mucus, amniotic fluid, and serum also change during pregnancy. In addition, cervical ripening of rabbit is accelerated by the administration of hyaluronan to the uterine cervix, collagenase activity is increased by the addition of hyaluronan to cell cultures of human myometrium in vitro, and cytokine production is promoted by adding hyaluronan to cultures of human uterine fibroblasts. On the other hand, hyaluronan level and collagen degradation activity are increased by administration of PGE2 to the uterine cervix. Therefore, hyaluronan appears to play an important role in uterine cervical ripening and dilatation. Generally, one of the physiological functions of hyaluronan is moisture retention. In addition, because hyaluronan synthase-2 knockout mouse cannot grow normally, it is thought that hyaluronan also plays an important role in organ maintenance. Recently it has been reported that the physiological functions of hyaluronan vary depending on its molecular weight. It is generally known that cervical hyaluronan increases rapidly at delivery, and makes parturition easy. However, in previous reports, the molecular weight of hyaluronan in the uterine cervix has not been taken into consideration. In this study, the molecular weight of hyaluronan in rabbit uterine cervix during late pregnancy was examined, and the uterine cervical ripening and dilatation activities of hyaluronan were investigated in vivo and in vitro.