A spontaneous induction of fetal membrane prostaglandin production precedes clinical labour

Abstract

Fetal membranes from term human pregnancies produce prostaglandins, and may respond to bacterial endotoxin or interleukin-1ß (IL-1ß) with increased prostaglandin E2 (PGE2) production. The effects of endotoxin persisted for up to 24 h, whereas those of IL-1ß were maximal 4-8 h after addition. The maximum levels of PGE2 (200-350 pg/ml) were similar in all experiments, and were independent of the stimulus used. Not all tissues responded to these stimuli; those which did not had basal levels of PGE2 production of 200-350 pg/ml, which was not further increased by endotoxin or IL-1ß. The basal production from these tissues was therefore similar to the maximal production from those tissues which responded to endotoxin or IL-1ß. The high basal production of PGE2 was attributed to prior in vivo activation of the membranes such that PGE2 synthesis could not be further stimulated in vitro. Overnight pretreatment with aspirin decreased basal PGE2 production from these activated membranes to <100 pg/ml/4 h during subsequent culture in aspirin-free medium. Both endotoxin and IL-1ß increased PGE2 production from the activated aspirin-pretreated membranes during this culture time, but this was transient as after 12 h of culture basal PGE2 production rose to over 200 pg/ml despite aspirin pretreatment.

Gingival crevicular fluid prostaglandin E2 level as a predictor of preterm low birth weight: a pilot investigation

“…Serum PGE 2 levels, which peaked during onset of labor, were reduced significantly after parturition. This is in accord with earlier studies demonstrating that the serum PGE 2 level increases at onset of labor (7,18). The results of different studies should be interpreted considering the characteristics of the study population, the methods of sample collection, the clinical status of patients at the time of sample collection, the time point at which the samples were collected, and the method used for estimation of PGE 2.…”

“…High levels of cycloxygenase-2 are expressed in fetal membranes prior to labor (7). After parturition, involution of various intrauterine tissues occurs, thus restoring the serum PGE 2 level to normal.…”

“…Some reports have suggested that the serum level of prostaglandin E 2 (PGE 2 ) increases at onset of labor (7). Periodontal infections, which serve as a reservoir of inflammatory mediators such as PGE 2 , may pose a threat to the fetal-placental unit.…”

Functional Screening of TLRs in Human Amniotic Epithelial Cells

“…The causes of PTB are multiple, but intra-amniotic infection and chorioamnionitis are thought to be a major cause of spontaneous preterm labor (PTL) and preterm premature rupture of the fetal membranes (PPROM). Extensive data from the literature have reported mechanisms involving a feed-forward loop network in normal parturition, where proinflammatory cytokines are able to stimulate production of PGs and thereby uterine contractions and to upregulate matrix metalloproteinase (MMP) activation and programmed cell death (apoptosis), leading to the weakening and the rupture of the fetal membranes (2)(3)(4)(5).…”

Regulation of prostaglandin production in intact fetal membranes by interleukin-1 and its receptor antagonist

“…Disks of intact tissue were cut using a sharpened punch and cultured in Medium 199 supplemented with ITS (insulin, transferrin, selenium and linoleic acid, all at 0·63 mg/ml, and BSA at 0·13 mg/ml; Sigma) in multiwell tissue culture plates for 24 h at 37 C in an atmosphere of 5% CO 2 /95% air. The medium was also supplemented with 1 mM aspirin, as we have shown that fetal membranes may be preactivated and spontaneously release high levels of PGE 2 (Brown et al 1998). After this time the medium was changed, the tissue washed with medium containing no aspirin, and incubated with or without IL-1 , IL-1 or IL-1ra or combinations of these for time periods stated in the Results section.…”