CONTEXT:The importance of prostaglandin (PG) signaling pathways to the maintenance of pregnancy and initiation of labor is well recognized. However, the complexity of these pathways and the mechanism(s) of their coordinated regulation in physiological and pathological conditions are only now being appreciated.OBJECTIVES:In this report we provide new evidence of a complete pathway for the biosynthesis and actions of PGD(2) and its metabolites within human gestational tissues.MATERIALS AND METHODS:Using immunohistochemistry and Northern and Western blotting, we demonstrate the dynamic regulation of H-type PGD synthase (PGDS) in placenta during gestation; in contrast, L-type PGDS and its PG products were detected in amniotic fluid, with increased amounts associated with labor.RESULTS:Placental tissues were shown to express both forms of the PGD(2) receptor identified to date, D prostanoid(1) (DP(1)) and DP(2)/chemotactic receptor on type 2 helper T cells, with a distribution consistent with the villous placenta being a major target, as well as source, of PGD(2). In vitro, placental PGD(2) production was shown to be stimulated upon inflammatory activation, whereas PGD(2) and its J series metabolites exerted potent inhibitory effects on placental cytokine production.CONCLUSIONS:These findings suggest that PGDS-derived prostanoids play important physiological roles in the placenta, such as immunoregulation and feto-placental communication, while potentially having a regulatory role in the processes of parturition.

Abstract Intra-amniotic secretion and abundance of epithelial cell-derived neutrophil-activating peptide (ENA)-78, a potent chemoattractant and activator of neutrophils, was studied in the context of term and preterm parturition. Staining of ENA-78 immunoperoxidase was localized predominantly to chorionic trophoblasts and amniotic epithelium in term and preterm gestational membranes, with weaker and less consistent staining in decidual cells. The abundance of ENA-78 in membrane tissue homogenates was significantly increased (∼4-fold) with term labor in amnion (n = 15), and with preterm labor (∼30-fold) in amnion and choriodecidua (n = 31). In amnion tissue homogenate extracts, ENA-78 levels were positively correlated with the degree of leukocyte infiltration (r2 = 0.481). In amniotic fluids, median ENA-78 levels from pregnancies with preterm labor without intra-amniotic infection were significantly lower (P < 0.01 by ANOVA) than those from pregnancies with preterm deliveries with infection; levels in samples derived from term pregnancies were similar before and after labor. Production of ENA-78 by amnion monolayers was stimulated in a concentration-dependent fashion by both interleukin-1β and tumor necrosis factor α. Production of ENA-78 by choriodecidual explants was increased modestly after 2–4 h of exposure to lipopolysaccharide (5 μg/ml). An immunoreactive doublet (∼8 kDa) was detected in choriodecidual explant-conditioned media by immunoblotting. We conclude that ENA-78, derived from the gestational membranes, is present in increased abundance in the amniotic cavity in response to intrauterine infection and, hence, may play a role in the mechanism of infection-driven preterm birth and rupture of membranes secondary to leukocyte recruitment and activation.

We have studied TNF-related apoptosis-inducing ligand (TRAIL) and its membrane-bound (R1-R4) and soluble receptors [osteoprotegerin (OPG)] in gestational membranes to assess their significance in preterm parturition and premature rupture of membranes (PROM). TRAIL was detected by ELISA in extracts of term choriodecidual (but not amnion) tissues and explant-conditioned media. Concentrations of OPG (determined using ELISA) in gestational membranes were 20- to 50-fold greater than those of TRAIL. Median OPG concentrations in amniotic fluid (AF) at 15-17 wk gestation were similar to those at term before and during labor, whereas levels in pregnancies sampled preterm were significantly elevated. OPG levels in AF from women with preterm PROM were similar to those from women in preterm labor. In contrast, in pooled AF samples (n = 23-33), TRAIL concentrations at term with and without labor were elevated compared with samples from preterm deliveries. TRAIL-R3 and -R4 decoy receptors were detected in term amnion and choriodecidual extracts by immunoblotting and were localized by immunohistochemistry to amnion epithelial cells and chorionic trophoblasts. TRAIL (100 ng/ml) had little or no effect on amnion or choriodecidual cell viability or apoptosis, although these tissues responded to TNF-alpha with increased prostaglandin E(2) production. Our findings suggest that OPG is abundant in gestational membranes and, in concert with TRAIL decoy receptors, may protect resident cells of the fetal membranes against the proapoptotic effects of TRAIL and other related ligands during pregnancy.

The elaboration of cytokines, chemokines and immunomodulatory proteins in the placenta and gestational membranes has been extensively investigated in the context of both normal and abnormal pregnancy and delivery. Patterns of expression of cytokines in the foetal membranes and decidua suggest that inflammatory activation occurs modestly with term labour, but much more robustly in preterm delivery, particularly in the presence of intrauterine infection. Enhanced chemokine expression, particularly evident in deliveries with an infected amniotic cavity, is presumably responsible for recruiting infiltrating leukocytes into the membranes thereby amplifying the inflammatory process and hastening membrane rupture and delivery. Anti-inflammatory cytokines suppress inflammatory reactions in the placenta, but under some circumstances may act in a pro-inflammatory fashion in the membranes. Intracellular signalling by cytokines is modulated by proteins such as SOCS (Silencer Of Cytokine Signalling)-1, -2 and -3. Changes in the abundance of these proteins occur with term labour, implicating them as modulators of cytokine actions around the time of parturition. Prostaglandins, released by the membranes in response to stretch and the actions of pro-inflammatory cytokines, act not only upon the myometrium and cervix, but may also exert paracrine/autocrine effects on cell viability and matrix protein integrity. The localization and regulation of prostanoid isomerases, responsible for converting PGH(2) (derived from prostaglandin H synthase-1 and -2) to bioactive prostanoids, are being studied in these tissues, particularly in the context of cytokine interactions. Although the gestational tissues are known to be sources of PGD(2), PGJ(2) and its derivatives, the regulation of production of these prostaglandins has yet to be studied in any detail and their actions, which may include apoptosis and suppression of inflammation, remain poorly defined. A more complete understanding of these aspects of cytokine-prostaglandin interactions in pregnancy and parturition will, no doubt, unfold as current studies come to fruition.

Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear receptors that are involved in lipid metabolism, differentiation, proliferation, cell death, and inflammation. Three subtypes have been identified: PPAR-alpha, -delta, and -gamma. We have previously shown presence of PPAR-gamma mRNA in the amnion, choriodecidua, and placenta, and its level of expression was unchanged with labor. To evaluate whether PPAR-alpha and -delta subtypes are present in intrauterine tissues, placentae were obtained from women at term after spontaneous vaginal delivery (TSL; n = 15) and elective caesarean section before labor (TNL; n = 15). Northern blot analyses were used to evaluate the mRNA for PPARs. Activities of PPARs were assessed using JEG3 choriocarcinoma cells transfected with a PPAR-response element reporter construct (pTK-PPREx3-luc) and treated with PPAR ligands. The PPAR-gamma-specific ligand rosiglitazone induced PPAR response element (PPRE)-mediated activity in a concentration-dependent manner, whereas the PPAR-gamma-specific irreversible inhibitor GW9662 fully inhibited this induction. However, GW9662 only partially inhibited 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2))-induced luciferase activity, suggesting that 15d-PGJ2 may also activate either of the other isoforms. PPAR-alpha and -delta are expressed in the amnion, choriodecidua, and placental villous tissues. In the amnion, although for PPAR-alpha no significant difference in expression was observed with labor, PPAR-delta expression increased significantly (p < 0.001). In the choriodecidua, expression of PPAR-&alpha; declined with labor (p < 0.01), whereas, as in the amnion, PPAR-delta expression increased (p < 0.05). In the placenta, both PPAR-&alpha; and -&delta; expression increased with labor (p < 0.005). The changes observed with labor suggest that regulation of PPAR expression and function may have roles to the mechanisms that maintain pregnancy or initiate labor.

The activity, expression and localization of the UDP-glucuronosyltransferases (UGTs) were investigated in human placenta at term. UGT activity (measured with the substrate 4-methylumbelliferone (4-MU)) was observed in all 25 placentas sampled and maximum velocity (V(max)) ranged 13-fold from 5.1+/-0.9 to 66.9+/-17.5 nmol/min/mg protein (mean+/-SD). Substrate affinity (K(m)) ranged 5-fold from 246+/-24 to 1124+/-422 microM. Using reverse transcriptase-polymerase chain reaction (RT-PCR), expression of the isoforms UGT2B4, 2B7, 2B10, 2B11 and 2B15 was observed in all (12/12) placentas sampled and expression of UGT2B17 was noted in 8/12 placentas. Northern analysis of the UGT2B7 isoform in 12 placentas revealed a 10-fold difference in expression with RT-PCR variability and the 13-fold variation observed in UGT activity. The presence of UGT2B4 and 2B7 proteins (52 and 56kDa, respectively) was demonstrated by Western blotting. The sites of placental UGT2B transcription (in situ hybridization) and protein expression (immunohistochemistry) were located in the syncytium of the placental trophoblasts bordering the placental villi. UGT1A proteins could not be observed with immunohistochemistry or Western blotting and expression could not be observed with RT-PCR. Our discovery of UGT expression and activity at the site of maternal-fetal exchange is consistent with a role for UGTs in detoxification of exogenous and endogenous ligands and the maintenance of placental function through clearance and regulation of steroid hormones.

Inflammatory processes are implicated in preterm labour (PTL). To identify potential novel markers for PTL, we have used commercial cDNA arrays to generate profiles of differential expression of inflammation-associated genes in gestational membranes with term and PTL. RNA for cDNA probe synthesis was isolated from reflected human amnion and choriodecidua membranes delivered following Caesarean section at term before the onset of labour (TNL, n = 4), spontaneous labour at term (TSL, n = 4), and PTL with and without chorioamnionitis (PTL(+INF) and PTL(-INF) respectively, n = 4 each). Profiles were displayed relative to TNL and statistical comparisons of TSL versus TNL and PTL(+INF) versus PTL(-INF) were performed. Elevated expression of chemokines macrophage inflammatory protein 1beta(MIP-1beta) and pulmonary and activation-regulated chemokine (PARC) was observed in PTL(+INF) compared to PTL(-INF) amnion and choriodecidua respectively (P = 0.03). Likewise, the cytokines oncostatin-M and pre-B cell enhancing factor (PBEF) were more highly expressed in PTL(+INF) compared with PTL(-INF) and in TSL compared with TNL respectively (P = 0.03). Conversely, inhibin A, tissue inhibitors of matrix metalloproteinase (TIMP)-3 and TIMP-4 were all significantly elevated in PTL(-INF) compared with PTL(+INF) (P = 0.03). Furthermore, differential expression patterns of classes of genes, grouped according to function (e.g. chemokines), were noted. The cDNA array approach holds promise for identification of new candidate markers or combinations thereof for prediction or diagnosis of PTL, as well as for increasing our understanding of the particular aetiologies involved.

OBJECTIVE:Our objective was to identify the novel or differential expression of growth or development associated genes in the human gestational membranes that might play roles in pregnancy or in term or preterm parturition.STUDY DESIGN:Complementary DNA arrays were probed with [alpha(33)P]dCTP-labeled-complementary DNA that was prepared from the RNA of reflected amnion and choriodecidua that represent term not-in-labor, term spontaneous labor, and preterm labor with and without chorioamnionitis (n = 4 per group). Differential expression (term not-in-labor vs term spontaneous labor or preterm labor with chorioamnionitis vs preterm labor without chorioamnionitis) was evaluated by Wilcoxon tests.RESULTS:All 16 amnion samples expressed angiogenic factors (endothelin-2 and -3, vascular endothelial growth factor, and vascular endothelial growth factor-B) and neurotrophic factors (ephrin-A2, ephrin receptors-A2, -B1, -B3, -B4, and -B5, neuropilin-2, p75/nerve growth factor receptor and semaphorin-F). In both amnion and choriodecidua, the expression of vascular endothelial growth factor and the angiopoietin receptor, Tie-2, were greater with term spontaneous labor than with term not-in-labor (P <.05); increased VEGF receptor-2 (flk-1) expression was observed in term spontaneous labor choriodecidua (P <.05) but not amnion. Ephrin-A1 expression increased with term spontaneous labor in both tissues (P <.05). Semaphorin-F expression decreased with preterm labor with chorioamnionitis in choriodecidua (P <.05), although the trend was not significant in amnion (P =.1).CONCLUSION:Neurotrophic and angiogenic factor genes are expressed in amnion and choriodecidual membranes. Several of the genes exhibit differential expression with labor at term or in association with infection preterm, which suggests roles in or associated with these processes.

Problem: The pro-inflammatory cytokine interleukin (IL)-1 beta has been shown to stimulate the production of prostaglandins (PG) in gestational tissues. Increased PG synthesis is considered a key step in the initiation of labor both at term and preterm. In this study. IL-1 beta mRNA in the uterus and gestational tissues of mice during mid to late pregnancy was studied to characterize its tissue specific as well as gestational age expression.Method of study: Gestational tissues (placenta. decidual cap and fetal membranes), uterus, and cervix were collected from pregnant mice during gestation. Total RNA was isolated and probed for the expression of IL-1 beta mRNA.Results: There was a significantly increased expression of IL-1 beta mRNA in the uterus on day 18 of pregnancy. In the decidual caps, there was increased expression of IL-1 beta mRNA on day 14 of pregnancy and a decrease in expression with the onset of labor. In the fetal membranes and placenta, IL-1 beta mRNA expression significantly increased on days 14 and 18 of pregnancy, respectively, and then remained elevated for the duration of pregnancy. In the cervix, there was a decrease in expression with labor onset.Conclusions: The increases in IL-1 beta mRNA in the fetal membranes and placenta late in pregnancy are consistent with a localized. tissue specific inflammatory activation involved in the initiation of parturition.

We evaluated the changes in mRNA expression of cytosolic phospholipase A(2)(cPLA(2)) and 15-hydroxyprostaglandin dehydrogenase (PGDH) in intrauterine and gestational tissues during mid-late murine pregnancy. Tissues (decidual caps, fetal membranes, and placentae, uterus, and cervix) were collected from pregnant mice at days 12, 14, 16, 18, and 19 (am and pm) of gestation. Total RNA was isolated and evaluated for cPLA(2)and PGDH expression by northern blot analysis normalized to GAPDH expression. Expression of mRNA for cPLA(2)increased in the placentae and decidual caps on day 18 and 19 pm, respectively. There was also increased expression for PGDH mRNA in the placenta and fetal membranes at the later stages of pregnancy. The tissue specific differences in expression of cPLA(2)and PGDH suggest that changes in enzymatic regulation of PG production and degradation may be crucial for the initiation of labour.

Apoptosis at the site of rupture has been proposed to play a role in premature rupture of the fetal membranes, a condition associated with increased risk of neonatal sepsis and preterm birth. We investigated the ability of peroxisome proliferator-activated receptor (PPAR)-γ ligands 15-deoxy-Δ12,14PGJ2 (15d-PGJ2), Δ12PGJ2, ciglitizone and rosiglitazone to induce apoptosis in the amnion-like WISH cell line. 15d-PGJ2 (10 μM) induced morphological characteristics of apoptosis within 2 h, with biochemical indices (caspase activation and substrate cleavage) following shortly after; maximum cell death (approximately 60%) was observed by 16 h, with an EC50 of approximately 7 μM 15d-PGJ2. Δ12-PGJ2 also induced apoptosis but was less potent and acted at a much slower rate. While ciglitizone also induced apoptosis, rosiglitazone had no effect on cell viability. The mechanism of induction of apoptosis by 15d-PGJ2 and Δ12PGJ2, which may be independent of PPAR-γ activation, requires further elucidation.

PROBLEM: The pro-inflammatory cytokine interleukin (IL)-1β has been shown to stimulate the production of prostaglandins (PG) in gestational tissues. Increased PG synthesis is considered a key step in the initiation of labor both at term and preterm. In this study, IL-1β mRNA in the uterus and gestational tissues of mice during mid to late pregnancy was studied to characterize its tissue specific as well as gestational age expression. METHOD OF STUDY: Gestational tissues (placenta, decidual cap and fetal membranes), uterus, and cervix were collected from pregnant mice during gestation. Total RNA was isolated and probed for the expression of IL-1β mRNA. RESULTS: There was a significantly increased expression of IL-1β mRNA in the uterus on day 18 of pregnancy. In the decidual caps, there was increased expression of IL-1β mRNA on day 14 of pregnancy and a decrease in expression with the onset of labor. In the fetal membranes and placenta, IL-1β mRNA expression significantly increased on days 14 and 18 of pregnancy, respectively, and then remained elevated for the duration of pregnancy. In the cervix, there was a decrease in expression with labor onset. CONCLUSIONS: The increases in IL-1β mRNA in the fetal membranes and placenta late in pregnancy are consistent with a localized, tissue specific inflammatory activation involved in the initiation of parturition.

These studies were undertaken to evaluate the changes in mRNA expression of prostaglandin H synthase (PGHS)-1 and -2 in murine gestational tissues during the latter half of pregnancy. Gestational tissues (decidual caps, membranes surrounding the fetus, and placentae), uterus, and cervix were collected from pregnant mice at days 12, 14, 16, 18, and 19 (am and pm) of gestation (n = 4), and total RNA was isolated and evaluated for PGHS-1 and PGHS-2 expression by northern blot analysis. Expression was normalized to GAPDH. There were no significant increases in PGHS-2 mRNA expression in any of the tissues studied through gestation. In contrast, expression of PGHS-1 mRNA increased significantly at term in the uterus and fetal membranes. In the placenta, mRNA for PGHS-1 was elevated at day 18 and remained elevated over the remainder of the study. These findings suggest that, in the mouse, increased production of PGs by uterine and intrauterine tissues during pregnancy is associated with up-regulation of PGHS-1 and not PGHS-2.

Prostaglandin-H-synthase-1 (PGHS-1), while constitutively expressed in most tissues, increases in abundance in human gestational membranes at term. This suggests that PGHS-1 may be up-regulated in preparation for labor, and thus might be a key determinant in timing labor onset. We conducted transient transfection experiments in amnion-derived AV3 cells utilizing pPGHS1CAT to identify substances that might regulate PGHS-1 expression in amnion. Transforming growth factor-β (1 ng/ml) and 15-deoxy-Δ12,14 prostaglandin J2 (1μM) significantly (P < 0.05) (33% and 44% respectively) increased PGHS-1 promoter activity. The activity decreased significantly (P < 0.05) in response to interleukin-1 (IL-1)β (1 ng/ml) (45%), tumor necrosis factor (TNF)-α (50 ng/ml) (34%), epidermal growth factor (10 ng/ml) (54%), phorbol myristate acetate (10 nM) (70%), IL-4 (10 ng/ml) (50%), IL-8 (100 ng/ml) (72%) and Activin A (25 ng/ml) (32%). Whether this degree of change in promoter activity leads to physiologically relevant alterations in the amounts of PGHS-1 present in cells remains to be determined.

We have evaluated the prostaglandin (PG) production and PG biosynthetic gene expression in a choriodecidual dispersed cell culture system. Cells dispersed from human choriodecidual membranes by dispase and trypsin digestion were evaluated after 1,3,5 and 7 days of culture for basal and tumour necrosis factor alpha (F-alpha) stimulated PGE2 production. The highest rates of production (P < 0.05) were obtained with cells treated after 3 days of culture, (3.7 +/- 1) x 10(2) pg PGE2 per 16 h per microg total cellular protein (mean +/- SEM), which was 3.9 times basal rate after 3 days culture. In choriodecidual cells treated after 3 days in culture, expression of prostaglandin endoperoxide H synthase-2 (PGHS-2) mRNAwas similarly responsive toTNF-alpha (3.9 times basal within 3 h of 30 ng/ml TNF-alpha) while there was little effect on PGHS-1 or cytosolic phospholipase A2 expression. Hence, the dispersed choriodecidual cell culture system described retainsTNF-alpha responsive PG biosynthetic capacity which is at least in part upregulated via increased expression of PGHS-2 mRNA.

RNA was extracted from human gestational membranes and villous placental tissue following spontaneous delivery (n=15) or elective caesarean section (n=15) at term. The samples were subjected to Northern analysis, using a 2kb cDNA probe for peroxisome proliferator activated receptor (PPAR)-γ. The mRNA was detectable in all choriodecidual and villous placental samples, irrespective of mode of delivery, but was only rarely detectable in the amnion. The JEG3 choriocarcinoma cell line also expressed PPARγ. In order to evaluate PPAR mediated transcriptional activation in JEG3 cells, the cells were transfected with pTK-PPREx3-luc, a PPAR response element (PPRE) containing luciferase reporter construct. Subsequent treatment with 10μm 15-deoxy-Δ12,14prostaglandin J2(15dPGJ2) resulted in an eight-fold stimulation of luciferase production relative to controls transfected with the same construct lacking the PPRE. This stimulation was concentration-dependent. These results suggest roles for PPARγ and its ligand in lipid, steroid and inflammatory mediator homeostasis and in remodelling of gestational tissues.

BioTechniquesVol. 28, No. 5 BenchmarksOpen AccessDirect Imaging of Northern Blots on an Optical Scanner Using Ethidium BromideRoberta L. Eykholt, Murray D. Mitchell & Keith W. MarvinRoberta L. Eykholt*Address correspondence to Roberta L. Eykholt, Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand. Internet: E-mail Address: r.eykholt@auckland.ac.nzFaculty of Medical and Health Sciences, University of Auckland, Auckland, New ZealandSearch for more papers by this author, Murray D. MitchellFaculty of Medical and Health Sciences, University of Auckland, Auckland, New ZealandSearch for more papers by this author & Keith W. MarvinFaculty of Medical and Health Sciences, University of Auckland, Auckland, New ZealandSearch for more papers by this authorPublished Online:29 Aug 2018https://doi.org/10.2144/00285bm07AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinkedInReddit FiguresReferencesRelatedDetailsCited ByHuman Mitochondrial Ribosomal Protein MRPL12 Interacts Directly with Mitochondrial RNA Polymerase to Modulate Mitochondrial Gene ExpressionJournal of Biological Chemistry, Vol. 282, No. 17Role of nuclear receptors and hepatocyte-enriched transcription factors for Ntcp repression in biliary obstruction in mouse liverAmerican Journal of Physiology-Gastrointestinal and Liver Physiology, Vol. 289, No. 5Heterocyst-Specific Expression of patB , a Gene Required for Nitrogen Fixation in Anabaena sp. Strain PCC 7120Journal of Bacteriology, Vol. 185, No. 7PCR-cloning and gene expression studies in common carp (Cyprinus carpio) insulin-like growth factor-IIBiochimica et Biophysica Acta (BBA) - Gene Structure and Expression, Vol. 1575, No. 1-3Newly Identified Cytochrome c Oxidase Operon in the Nitrogen-Fixing Cyanobacterium Anabaena sp. Strain PCC 7120 Specifically Induced in HeterocystsJournal of Bacteriology, Vol. 184, No. 9UDP-glucuronosyltransferase activity, expression and cellular localization in human placenta at termBiochemical Pharmacology, Vol. 63, No. 3Regulation of prostaglandin biosynthesis in dispersed choriodecidual cells in cultureProstaglandins, Leukotrienes and Essential Fatty Acids (PLEFA), Vol. 65, No. 5-6Glutamate Regulates Kainate-binding Protein Expression in Cultured Chick Bergmann Glia through an Activator Protein-1 Binding SiteJournal of Biological Chemistry, Vol. 275, No. 50 Vol. 28, No. 5 Follow us on social media for the latest updates Metrics Downloaded 258 times History Published online 29 August 2018 Published in print May 2000 Information© 2018 Author(s)PDF download

We have determined that prostaglandin H synthase-2 localises strongly to the nuclear membrane as well as being found in the endoplasmic reticulum in human amnion-derived WISH cells which have been stimulated with interleukin 1β and phorbol ester. This is consistent with findings in cells of non-reproductive origin. There is strong evidence that prostaglandin J2derivatives, which in other tissues exhibit tumour suppressing, antiproliferative and/or differentiation promoting activities, act through binding of intracellular receptors which then enter the nucleus. In addition, some arachidonic acid derivatives are clearly generated by enzymes at the nuclear envelope and localise to sites in nuclei or bind sites in nuclei. The WISH cell line will make an excellent system for studying these perinuclear intracellular prostanoid signaling mechanisms.

PROBLEM:Clinically useful tests for the prediction and diagnosis of preterm labor and delivery remain to be established. We have hypothesized that soluble intercellular adhesion molecule-1 (sICAM-1) in the cervicovaginal fluid of women with preterm labor may be a useful diagnostic tool.METHOD OF STUDY:The cervicovaginal fluid of 103 women between 24(0) and 33(6) weeks gestation with preterm contractions and intact membranes was assayed for sICAM-1.RESULTS:Elevated sICAM-1 concentrations predicted short intervals to delivery (area under receiver operator characteristic (ROC) curves, 0.70-0.72 for delivery within 3, 7 and 10 days), with high specificity. Characteristics for delivery within 3 days at a 3 ng/mL threshold for a positive test were sensitivity 33.3%, specificity 98.9%, and positive and negative predictive values of 75.0% and 93.9%, respectively. Predictive ability was independent of and complementary to that of fetal fibronectin (fFN).CONCLUSIONS:Measurement of sICAM-1 in cervicovaginal fluid has potential as a predictor of preterm delivery in women with symptoms of preterm labor, particularly in conjunction with fFN testing.