Endocrine and neuronal interactions in human cervical ripening

Abstract: Objective: To evaluate the hormonal and neuronal environment in human cervix during pregnancy and parturition. Methods: Cervical biopsy specimens were obtained transvaginally, and serum samples were drawn simultaneously. Enzyme immunoassays were used for receptor determinations, solution hybridization for mRNA analyses, radio immunoassay for serum estradiol and progesterone, indirect immunohistochemistry for neurochemical and cellular markers. Biochemically, the collagen concentration (hydroxyproline), collagen solubility in pepsin, and proteoglycan concentrations (Alcian Blue) were determined. Results and discussion: The concentrations of ER and PR were decreased after the gradual ripening until term, and further decreased after the final ripening at parturition. The IGF-I mRNA level was 4-fold increased at term, and was decreased to about half of this level after parturition. These changes coincided with a remodelling of the connective tissue. The final ripening at parturition was associated with a sharp decrease in the small proteoglycan (decorin) concentration, a tendency towards an increase in large proteoglycans (versican), and a tendency towards increased collagen solubility, despite an unchanged collagen concentration. PGE2 treatment was followed by steroid receptor and IGF-I mRNA concentrations, comparable to those, seen after spontaneous ripening. The collagen solubility was comparable despite a higher collagen concentration in comparison to spontaneous ripening. Antiprogestin (RU486) treatment was followed by a higher ER concentration and a tendency towards a higher serum estradiol level, in comparison to spontaneous ripening, while the levels of PR and IGF-I mRNA were unchanged in comparison to spontaneous ripening. The frequency of PGP 9.5 positive nerve fibers and cells was markedly increased at term, and slightly lower after parturition. The frequency and appearance of immunoreactivity for the neuropeptides CGRP, VIP, PHM-27 and NPY was changed at late pregnancy and further after parturition. The content of HLA-DR and protein S-100 positive dendritic cells was increased in the late pregnant group, slightly lower after parturition, and the lowest in the non-pregnant group. Conclusions: Cervical ripening in humans is related to local endocrine and neuronal changes, and to an activation of the immune system.