Cervical ripening after treatment with prostaglandin E2 or antiprogestin (RU486). Possible mechanisms in relation to gonadal steroids.

OBJECTIVE: To compare the mechanisms for cervical ripening after treatment with prostaglandin E2 or antiprogestin (RU486) to spontaneous cervical ripening, with focus on gonadal steroid receptors. STUDY DESIGN: Cervical biopsies were obtained from postpartal women after treatment with prostaglandin E2 (n=10), or antiprogestin (n=5). Postpartal women after spontaneous cervical ripening (n=10) served as controls. Levels of estrogen and progesterone receptors, their mRNAs, insulin-like growth factor I mRNA and serum estradiol and progesterone were quantitated. The collagen concentration and solubility by pepsin were determined. Statistical tests used were Kruskal-Wallis and Mann-Whitney U test. RESULTS: After prostaglandin E2 treatment the collagen concentration was higher (P<0.05) as compared to spontaneous ripening. After antiprogestin treatment the estrogen receptor concentration was higher (P<0.05) in comparison to spontaneous ripening. CONCLUSION: The elevated estrogen receptor concentration after antiprogestin treatment, in contrast to spontaneous ripening, and prostaglandin E2 treatment, indicates a that a receptor-mediated progesterone withdrawal does not explain the events behind spontaneous cervical ripening at parturition.

Cervical fetal fibronectin correlates to prostaglandin E2-induced cervical ripening and can be identified in cervical tissue.

OBJECTIVE: Our purpose was to investigate whether prostaglandin E2-induced cervical ripening can be related to changes in fetal fibronectin levels and whether fetal fibronectin can be detected by immunohistochemistry in amniotic and cervical tissue. STUDY DESIGN: Fetal fibronectin levels in cervical mucus were quantitated in 28 nulliparous term pregnant women with unfavorable cervical states before and after intracervical application of prostaglandin E2 gel. The concentration of fetal fibronectin was determined with use of an enzyme immunoassay. Cervical biopsy specimens and amniotic tissue for immunohistochemical analysis were obtained from three term pregnant women and after parturition in three women. Cervical biopsy specimens from two nonpregnant women served as controls. Immunohistochemical analysis was performed with antibodies directed toward fetal fibronectin. RESULTS: The fetal fibronectin level in cervical mucus was low in all women before prostaglandin E2 application. In women with a successful prostaglandin E2-induced ripening (i.e., an increase of cervical score with > or =3 points), a tenfold increase in the fetal fibronectin level was registered. In women with an insufficient cervical ripening after prostaglandin E2 treatment no significant increase in the fetal fibronectin level was registered. The immunohistochemical analyses have identified fetal fibronectin in the epithelial cells of the cervix uteri. CONCLUSION: Successful prostaglandin E2-induced cervical ripening seems to be related to a significant increase in cervical fetal fibronectin levels. Fetal fibronectin can be detected immunohistochemically in the pregnant human cervix.

Interleukin-8 is a mediator of the final cervical ripening in humans.

OBJECTIVE: The aim of the present study was to investigate the presence of interleukin-8 (IL-8) in the human cervix and whether the levels of interleukin-8 could be related to the ripening process during pregnancy. STUDY DESIGN: Cervical biopsies were obtained in twelve term pregnant and in eight vaginally delivered women. Seven non-pregnant fertile women served as controls. After homogenisation and centrifugation, IL-8 levels were determined in the supernatant by an enzyme-immunoassay (EIA). RESULTS: In women at term, the concentration of IL-8 increased six-fold from median 330 pg/ml to median 2190 pg/ml (P < 0.001). After the final cervical ripening it increased in additional 11-fold to median 26,100 pg/ml (P < 0.001). These changes are highly significant. CONCLUSION: To our knowledge, this is the first time IL-8 has been identified in human cervix. Our results support the involvement of IL-8 in the connective tissue remodelling during the final cervical ripening just before onset of labour.

Serum collagenase levels in relation to the state of the human cervix during pregnancy and labor.

OBJECTIVE: The purpose of our study was to investigate the role of collagenase in the cervical ripening and dilatation process in term pregnancy. STUDY DESIGN: Serum samples were obtained from nonpregnant women (n = 5) and term-pregnant women. The term-pregnant women were either admitted for elective cesarean section or labor induction (unfavorable cervix, n = 19; favorable cervix, n = 12) or in spontaneous, active labor (stiff and inelastic cervix, n = 7; soft compliant cervix, n = 8). Statistical analysis was performed with the Student t test. RESULTS: The nonpregnant women had low serum collagenase levels (5.2 +/- 0.7 micrograms collagen digested per minute per 100 ml serum, mean +/- SEM). At term but before labor, women with unripe cervices had higher collagenase levels (10.3 +/- 0.9). The women with ripe cervices had even higher serum collagenase levels (22.9 +/- 4.2; p < 0.001). During labor, women with stiff and inelastic cervices had lower serum collagenase levels compared with women with soft and compliant cervices (12.9 +/- 1.7 vs 28.0 +/- 4.2; p < 0.01). CONCLUSION: Serum collagenase during ripening at term and in active labor increases, supporting its active role in the ripening process.