RU486 inhibits synthesis of an endogenous inhibitor of cell arachidonate release from choriodecidua tissue

Abstract

Gravidin is a potent phospholipase A2 inhibitor that may contribute to the maintenance of human pregnancy. The aims of this study were to determine firstly, the site of gravidin synthesis within placental membranes and secondly, whether the antiprogestin compound, RU486, regulates synthesis. Membrane explants were taken from placentae, dissected and cultured in the presence of RU486, progesterone or inhibitors of DNA or protein synthesis and gravidin production was measured by a specific enzyme-linked immunosorbent assay. Production of gravidin was consistently greatest from choriodecidua compared with amnion and decidua. The antibiotics, cycloheximide and actinomycin D inhibited production of gravidin. The progesterone receptor antagonist RU486 at 10(-8) and 10(-7) M reduced gravidin production to 55 and 39% of the control value in membranes cultured after and before the onset of labour respectively. Progesterone at 10(-6) M stimulated gravidin production by 47% after the onset of labour. The increase in gravidin production was correlated with progesterone concentration (r = 0.47, F = 6.38, P = 0.019) in labour tissue. We conclude that the data are consistent with the hypothesis that gravidin production may be partially regulated by progesterone.

Soluble TLR2 Is Present in Human Amniotic Fluid and Modulates the Intraamniotic Inflammatory Response to Infection

“…Monensin is a Na ϩ ionophore that blocks posttranslational processing events that take place in internal cellular compartments without affecting activities at the cell surface (32). Conversely, cycloheximide is an antibiotic that inhibits de novo protein synthesis by blocking translation of RNA (33). We found that during the course of 24-h incubation, sTLR2 accumulated in the explant medium villous tissue.…”

“…A flowchart of the women enrolled in the study and subgroups of samples analyzed are presented in the supplemental Fig. 4 Amniotic fluid was retrieved from 109 women who had a clinically indicated amniocentesis in the following different populations: second trimester normal genetic karyotyping (GA median (range), 19 (15)(16)(17)(18)(19)(20)(21)(22)(23) wk, n ϭ 14), third trimester fetal lung maturity testing before cesarean delivery (GA, 37 (35)(36)(37)(38)(39) wk, n ϭ 14), and women admitted with symptoms of preterm labor who had an amniocentesis to rule out infection (GA, 28 (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36) wk, n ϭ 81). To avoid selection bias, women in this last group were selected from a prospective cohort of 463 consecutive patients enrolled at Yale New Haven Hospital from March 2004 to June 2008.…”