Impaired leukocyte influx in cervix of postterm women not responding to prostaglandin priming

<p>Abstract</p> <p>Background</p> <p>Prolonged pregnancies are associated with increased rate of maternal and fetal complications. Post term women could be divided into at least two subgroups, one where parturition is possible to induce by prostaglandins and one where it is not. Our aim was to study parameters in cervical biopsies in women with spontaneous delivery at term (controls) and compare to those that are successfully induced post term (responders), and those that are not induced (non-responders), by local prostaglandin treatment.</p> <p>Methods</p> <p>Stromal parameters examined in this study were the accumulation of leukocytes (CD45, CD68), mRNAs and/or proteins for the extracellular matrix degrading enzymes (matrix metalloproteinase (MMP)-2, MMP-8 and MMP-9), their inhibitors (tissue inhibitor of MMP (TIMP)-1 and TIMP-2), interleukin-8 (IL-8), the platelet activating factor-receptor (PAF-R), syndecan-1 and estrogen binding receptors (estrogen receptor (ER)α, ERβ and G-coupled protein receptor (GPR) 30) as well as the proliferation marker Ki-67.</p> <p>Results</p> <p>The influx of leukocytes as assessed by CD45 was strongest in the responders, thereafter in the controls and significantly lower in the non-responders. IL-8, PAF-R and MMP-9, all predominantly expressed in leukocytes, showed significantly reduced immunostaining in the group of non-responders, while ERα and GPR30 were more abundant in the non-responders, as compared to the controls.</p> <p>Conclusion</p> <p>The impaired leukocyte influx, as reflected by the reduced number of CD45 positive cells as well as decreased immunostaining of IL-8, PAF-R and MMP-9 in the non-responders, could be one explanation of the failed ripening of the cervix in post term women. If the decreased leukocyte influx is a primary explanation to absent ripening or secondary, as a result of other factors, is yet to be established.</p

Interleukin-8 is involved in cervical dilatation but not in prelabour cervical ripening

Our aim was to determine the amount and source of interleukin (IL)-8 and to study IL-8 receptor expression in the human cervix during pregnancy and after labour. Cervical biopsies were obtained from six non-pregnant women, eight women undergoing pregnancy termination, 17 women undergoing elective caesarean section and 11 women after vaginal delivery. IL-8 levels were compared in women with and without a ripe cervix, as determined by cervical Bishop score and cervicovaginal fetal fibronectin levels. Levels of IL-8 and IL-1β, a regulator of IL-8 expression, were determined by enzyme-linked immunosorbent assay (ELISA). IL-8, IL-1β and IL-8 receptor proteins were localized by immunohistochemistry. Compared with late pregnancy, IL-8 levels increased after labour and vaginal delivery (P < 0·01) but there was no correlation with cervical ripening. IL-8 was localized to stromal cells, macrophages and granulocytes. There were no significant differences in IL-1β levels between groups. IL-8 receptors were expressed primarily on granulocytes and macrophages after vaginal delivery. We conclude that IL-8 is involved in cervical dilatation but not in cervical ripening

Rapid effect of progesterone on transepithelial resistance of human fetal membranes: Evidence for non-genomic action

1. The factors that regulate human fetal membrane transport mechanisms are unknown. The aim of the present study was to investigate the effect of progesterone on transepithelial electrical resistance (R-TE) in the human amniochorion. 2. Fetal membranes from uncomplicated term pregnancies were obtained immediately after vaginal or Caesarean deliveries. Intact pieces were mounted as planar sheets separating an Ussing chamber. Progesterone (10(-4) to 10(-7) mol/L), mifepristone (10(-4) to 10(-8) mol/L) and combinations of progesterone plus mifepristone were applied to the chambers facing the fetal or maternal sides of the membrane. The R-TE was measured before and 1, 5, 10, 15, 20, 25, 30, 45 and 60 min after each solution was added (at 37 degrees C). The R-TE was calculated in Omega.cm(2), according to Ohm's law. 3. The mean (+/- SEM) basal value of R-TE before the application of any substance in all experiments was 29.1 +/- 0.4 Omega.cm(2). The net change in the R-TE (Delta R-TE) in relation to the basal value was calculated in each experiment. Progesterone, mifepristone and the combination of progesterone and mifepristone induced a rapid, surge-type increase in R-TE during the 1st min on both sides of the membrane. The combination of progesterone plus mifepristone exerted a synergistic action. The effect was stronger on the fetal side than on the maternal side for all substances tested (P < 0.05). The highest Delta R-TE during the 1st min on the fetal side was seen with the combination of progesterone plus mifepristone (4.0 +/- 0.3 Omega.cm(2)) and the lowest Delta R-TE occurred with mifepristone (1.5 +/- 0.1 Omega.cm(2)). 4. The present results demonstrated that the R-TE of human fetal membranes increases rapidly in response to progesterone. It is possible that changes in R-TE play a role in the control of membrane permeability during pregnancy