Human Decidual Tissue Research Articles

Profiling Chemokines, Cytokines and Growth Factors in Human Early Pregnancy Decidua By Protein Array

In human decidua, a significant increase of leukocytes including CD56(++)CD16(-) uterine natural killer (uNK) cells and CD14(+) monocytes has been observed with the onset of pregnancy. The mechanisms required for the recruitment of those cells to the uterus are still under debate. Cytokines and chemokines have been suggested as key factors for the regulation of these complex cellular migration and interaction processes. Investigation of the expression patterns of cytokines, chemokines and growth factors in human decidual tissue (7-8 weeks of gestation) was performed by protein array analysis. Isolated decidual leukocytes, i.e. CD56(++)CD16(-) uNK, CD14(+) monocytes as well as cytotrophoblast (CTB) and stromal cells were tested separately. This analysis revealed the production of monocyte attracting chemokines (GRO, MCP-1), angiogenetic substances (EGF, VEGF, Angiogenin) as well as granulocyte activating peptides (ENA-78, IL-1beta, RANTES, IL-8) by decidual tissue and its cell subsets. The observed pattern supports the role of decidua as a tissue which promotes angiogenesis, attracts monocytes and modulates the function of the latter.

Lack of Site-Specific Production of Decidual Alpha-2 Macroglobulin in Human Pregnancy

Alpha-2 Macroglobulin (A2M) is a protease inhibitor that is present in both human and rat decidual tissue. In mice, decidual A2M prevents excessive trophoblastic invasion; however, its role in human decidual tissue is unknown. It is possible that A2M may also influence trophoblast invasion in human pregnancy, which would be reflected in increased A2M production in decidua basalis. The aim of the current study was to determine and compare A2M production from first trimester human decidua basalis and decidua parietalis. Human decidual tissues were obtained from patients undergoing surgical termination at 9 to 12 gestational weeks. Strips of decidua basalis and decidua parietalis were obtained by uterine curettage under real-time ultrasound guidance. Tissue samples were fixed in 10% formalin or snap-frozen for immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, respectively. Protein and mRNA production between the two sites were compared using the Mann-Whitney U test. Paired basal and parietal decidua were analyzed by immunohistochemistry (n = 9) and by RT-PCR (n = 10). There was no significant difference in A2M mRNA expression between decidua basalis and decidua parietalis (P = .5). Immunohistochemical staining intensity for A2M protein was significantly higher in basalis than in parietalis (P = .004), but the extent of positively stained cells were not significantly different (P = .051). Strong A2M staining in decidua basalis was mainly localized in the intracellular storage vesicles, which may suggest a role of A2M in this site. We conclude that the expression pattern of A2M in human decidua basalis and decidua parietalis is not consistent with an important role of this gene during the observed gestational period. Contrary to its role in rodent implantation, A2M is probably not involved in regulating human implantation and trophoblastic invasion during this gestational window frame.

Objective prioritization of positional candidate genes at a quantitative trait locus for pre-eclampsia on 2q22

Pre-eclampsia/eclampsia (PE/E) is a common, serious medical disorder of human pregnancy. Familial association of PE/E has been recognized for decades, but the genetics are complex and poorly understood. In an attempt to identify PE/E susceptibility genes, we embarked on a positional cloning strategy using 34 Australian and New Zealand PE/E pedigrees. An initial 10-cM resolution genome scan revealed a putative susceptibility locus spanning a broad region on chromosome 2 that overlaps an independently determined linkage signal seen in Icelandic PE pedigrees. Subsequent fine mapping using 25 additional short tandem repeat (STR) markers in this region and non-parametric multipoint linkage analysis did not change the overall position. Under a strict diagnosis of PE, we obtained significant evidence of linkage on 2q with a peak log-of-odds ratio score (LOD) of 3.43 near marker D2S151 at 155 cM. To prioritize positional candidate genes at the 2q locus for detailed analysis, we applied an objective prioritization strategy that integrates quantitative bioinformatics, assessment of differential gene expression and association analysis of single-nucleotide polymorphisms (SNPs). Highest priority was assigned to the activin receptor gene ACVR2. This gene also showed >10-fold differential gene expression in human decidual tissue from normotensive and PE individuals. We genotyped five known SNPs in this gene in our pedigrees and performed tests for association and linkage disequilibrium. One SNP (rs1424954) showed strong preliminary evidence of association with PE (P = 0.007), whereas two others (rs1364658 and rs1895694) exhibited nominal evidence (P < 0.05). Haplotype analysis revealed no additional association information. There was evidence of weak linkage disequilibrium among these SNPs. The highest observed LD occurred between the two strongest associated SNPs, suggesting that the observed signals may be the signature of an observed functional variant.

Human Decidua‐associated Protein 200 Neutralizes the Detrimental Effect of Serum Containing Antiphospholipid Antibodies on Fetal Survival in the Rat

We wanted to examine whether the detrimental effect of serum containing antiphospholipid (APL) antibodies on rat pregnancy outcome can be neutralized by addition of human decidua-associated protein (hDP) 200, a kind of rheumatoid factor, extracted from decidual tissue. Fifty microliters of pooled serum, obtained from women having anticardiolipin antibody and lupus anticoagulant and presenting with APL antibody syndrome, added with 100 microL of immunoaffinity purified hDP200 was injected into unilateral uterine horn of each rat on day L5 of rat pregnancy. The contralateral uterine horn was used for injection of 50 microL APL positive serum added with physiologic saline as a control. The rats were killed on day L14, and the uterus of each rat was inspected for the presence of live and resorbed fetuses. The addition of hDP200 to APL positive serum before the intrauterine injection neutralized the detrimental effect of APL serum on fetal resorption rate. Although the neutralizing effect was demonstrated following the addition of hDP200 and immediate intrauterine injection (a decrease in fetal resorption rate, P = 0.004), still the effect was more impressive following the addition of hDP200 and incubation period of 24 hr before the injection, thus causing a significant increase in the number of normal embryos and a significant decrease in fetal resorption rate (P < 0.001). Human decidua-associated protein 200, extracted from human decidual tissue neutralizes the detrimental effect of serum containing APL antibodies in an experimental rat model. Further studies are needed to prove this finding.

Fibroblast growth factor-10 and fibroblast growth factor receptors 1–4: expression and peptide localization in human decidua and placenta

The development of the chorionic villous tree into a complex and organized ramified tubular network can be termed branching morphogenesis. Studying the molecular mechanisms involved in this process may contribute to the understanding of pregnancy complications such as preeclampsia. We hypothesized that fibroblast growth factor-10 (FGF-10) and fibroblast growth factor receptors 1–4 (FGFR 1–4) are expressed in human decidual and placental tissues. We analyzed the expression of FGF-10 and FGFRs 1–4 in 1st, 2nd and 3rd trimester placentas, as well as in decidua. RT-PCR and immunohistochemistry were employed to study mRNA and protein expression. FGF-10 was expressed by decidual cells and by cytotrophoblasts of the cytotrophoblast columns during all three trimesters. FGFR 1–4 were expressed in the placenta but not in the decidua. Placental expression of FGFRs was temporally regulated: In 1st trimester placentas, FGFR 1–4 were expressed by Hofbauer cells, FGFR-1 and FGFR-4 were expressed in cytotrophoblast columns, and the latter was also expressed by syncytiotrophoblasts. Similar expression was seen in 2nd trimester placentas with additional expression of FGFR-1 in blood vessel walls. The expression of FGFR-1 and FGFR-4 in the 3rd trimester was comparable to that seen in the 2nd trimester. The expression of FGF-10, FGFR-1 and FGFR-4 in the maternal–fetal interphase suggests their role in decidual-trophoblast interaction. The abundance of FGFR expression in Hofbauer cells implies that mesenchymal-trophoblast interaction is important for regulation of villous development.

Expression pattern of collagen XVIII and its cleavage product, the angiogenesis inhibitor endostatin, at the fetal–maternal interface

Endostatin, the C-terminal fragment of the basement membrane protein collagen XVIII regulates epithelial cell migration and impairs tumour growth by inhibiting angiogenesis. Here, we investigated the expression pattern of collagen XVIII/endostatin in human placental and decidual tissues of various ages of gestation as well as in primary villous cytotrophoblasts, trophoblast cell lines, and villous explant cultures differentiating along the invasive pathway. RT-PCR analysis revealed production of collagen XVIII mRNA in total placenta and decidua of early and late pregnancy and in SGHPL-5 and HTR-8/Svneo cells. Collagen XVIII transcripts were absent from purified extravillous trophoblasts and syncytialising trophoblast cultures. Accordingly, an antibody against a protein domain common to different collagen XVIII isoforms detected the 180 kDa protein in villous and decidual tissue and cultivated placental fibroblasts but not in the different isolated trophoblast cell types. Immunohistochemical analyses localised collagen XVIII to villous basement membranes and to the endothelium as well as to placental and decidual stromal cells. Interestingly, expression of various forms of endostatin (20 and 26 kDa) was detected in placenta and decidua using Western blot analyses. Moreover, supplementation of recombinant endostatin increased MMP-2 expression in villous explant cultures and SGHPL-5 cells suggesting that the inhibitor may modulate extravillous trophoblast differentiation.

Indoleamine 2,3-dioxygenase (IDO) expression in invasive extravillous trophoblast supports role of the enzyme for materno-fetal tolerance

It is still not understood how the fetus escapes from being attacked by the maternal immune system. Recent reports based on mouse and in vitro models have suggested that the enzyme indoleamine 2,3-dioxygenase (IDO) is important for materno-fetal tolerance. IDO activity in the human placenta is known to be high and might lead to inhibition of T-cell proliferation, thus preventing fetal tissue from rejection by the maternal immune system. In an attempt to elucidate the precise location of IDO at the feto-maternal junctional zone, we investigated human placental and decidual tissue of first and third trimester of pregnancy using an immunohistochemical approach. In placental tissues, only syncytiotrophoblast and endothelial cells showed moderate expression of IDO. This pattern was observed regardless of whether first or third trimester tissue was investigated. In early and term decidua, cells with the typical morphology of invasive extravillous trophoblast (EVT) were strongly positive for IDO. Blocking immunohistochemical experiments with cytokeratin and IDO antibodies identified invasive EVT as the location of predominant IDO expression. Since EVT are the fetal cells with the closest contact to the maternal immune system, our results suggest that it is EVT which protects the fetus from rejection by downregulating local maternal T-cell responses.

Platelet-activating factor inhibits the secretion of platelet-activating factor acetylhydrolase by human decidual macrophages.

To clarify the role of platelet-activating factor (PAF) in parturition, the effects of PAF on the secretion of PAF-acetylhydrolase (PAF-AH), a PAF-inactivating enzyme, by decidual macrophage populations were examined. The cells were isolated from human decidual tissue by enzymatic digestion, Ficoll-Paque centrifugation, or flow cytometric sorting. The nonhydrolyzable agonist of PAF, carbamyl-PAF (C-PAF), inhibited the secretion of PAF-AH by either decidual cells or flow cytometrically purified decidual macrophages. A specific PAF receptor antagonist, WEB 2086, blocked the C-PAF-induced inhibition. Lyso-PAF, a metabolite of PAF, had no effect on the enzyme secretion. An intracellular calcium channel blocker, bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid, tetra(acetoxymethyl)-ester, partially blocked the inhibition by C-PAF, whereas extracellular calcium channel blockers, nifedipine and verapamil, were without effect. The inhibitory effect of C-PAF was also partially blocked by protein kinase C (PKC) inhibitors, sphingosine and H-7. A PKC activator, 12-O-tetradecanoylphobol 13-acetate, decreased the secretion of PAF-AH. The decrease was abolished by the addition of sphingosine and H-7. It is suggested that PAF inhibits the PAF-AH secretion by decidual macrophages and that the inhibitory action is mediated by a signal transduction mechanism involving intracellular calcium and PKC.

Cyclic AMP enhances the expression of an extravillous trophoblast marker, melanoma cell adhesion molecule, in choriocarcinoma cell JEG3 and human chorionic villous explant cultures.

Human trophoblasts consist of two main cell lineages, villous trophoblasts (VT) and extravillous trophoblasts (EVT). To identify the molecules which are involved in EVT differentiation, we have raised a monoclonal antibody (mAb) designated CHL1, by immunizing a mouse against human chorion laeve which is composed of EVT. By immunohistochemical analysis, the CHL1 antigen was found to be expressed on the majority of EVT but not on VT in addition to its expression on endothelial and myometrial cells. A subsequent cDNA panning method revealed that the CHL1 antigen was identical to melanoma cell adhesion molecule (MCAM, Mel-CAM, S-endo 1 or MUC18/CD146), which has been previously reported as one of the EVT markers. MCAM expression on JEG3 cells, a human choriocarcinoma-derived cell line, was significantly enhanced when they were co-cultured with isolated human decidual tissue. Various cytokines and growth factors that were reportedly present in decidual tissue failed to increase MCAM expression in JEG3 cells, but decidua-induced MCAM expression in JEG3 cells was attenuated by the addition of protein kinase A inhibitor H89. In addition, cAMP, which is known to stimulate differentiation of VT, enhanced MCAM expression in JEG3 cells. Its promoting effect on MCAM expression was also observed in human chorionic villous explant cultures. These findings suggest that a cAMP-dependent intracytoplasmic signalling pathway is involved in the differentiation mechanism of human EVT.

Expression of beta hCG and alpha CG mRNA and hCG hormone in human decidual tissue in patients during tubal pregnancy.

We recently showed that endometrial tissue produces hCG during the secretory phase of the menstrual cycle. Based on these findings, we hypothesized that the decidua should also be able to secrete hCG. We examined the decidualized endometrium of patients with extrauterine pregnancies. Decidual specimens were obtained for mRNA extraction and paraffin embedding from 24 patients that were between weeks 6-11 of tubal pregnancy. Tissues were evaluated and classified into one of three groups based on the endometrial differentiation that took place prior to conception: (A) high secretory transformation, (B) diminished transformation with restricted decidualization and (C) inferior endometrial proliferation. Decidual gland hCG secretion was demonstrated immunohistochemically and by Western blotting. Serum hCG levels were higher (P < 0.0001) in patients from group A than group C. mRNA expression of both the beta subunit (beta-hCG) and alpha subunit (alpha-CG) was determined by RT-PCR. Furthermore, the specificity of beta-hCG amplification was confirmed by restriction enzymes. beta-LH amplification was not found. Moreover, the degree of endometrial transformation and the level of decidualization was found to correlate with hCG hormone staining and beta-hCG mRNA expression. hCG protein in the decidua was present in the glands of the compact layer and in the spongy layer, and was more pronounced in previously transformed high secretory endometrium than in inferior endometrium. In conclusion, this study provides the first evidence that hCG is produced in the decidua of patients during extrauterine pregnancies and might play a possible paracrine role.

Human malignant cell death by apoptosis-inducing nucleosides from the decidua derived CD57 +HLA-DR bright natural suppressor cell line

The CD57 +HLA-DR bright natural suppressor (57.DR-NS) cell line derived from human decidual tissue mediated apoptosis of human leukemia Molt4 and carcinoma BeWo/GCIY cells but not human fibroblast WI-38 cells, and apoptosis-inducing nucleosides (AINs) appeared to be involved. Six AINs were released into 57.DR-NS cell culture media and were isolated by the combination of physicochemical procedures of C18 preparative column, thin layer chromatography (TLC) and high pressure liquid chromatography (HPLC). Subsequently, we demonstrated that AINs could induce apoptosis in the human malignant Molt4/BeWo/GCIY cell line but not human normal WI-38 fibroblasts. Apoptosis was characterized by DNA strand breaks and activation of the caspase cascade, especially caspase-3. The administration of AINs into GCIY tumor bearing SCID mice culminated in suppression of tumor growth due to apoptosis of tumor cells.

Expression of glucose transporter 1 in human endometrial and decidual tissue

Regulation of endometrial glucose transport is important for the decidualization process. Therefore ,we have examined the expression of the glucose transporter protein isoform 1 (GLUT1) in endometrial samples during the menstrual cycle and in decidual tissue by immunohistochemistry ,and GLUT1 mRNA by RNase protection assays. GLUT1 protein was not detected in proliferative endometrial samples ,but was highly expressed in decidual tissue. Placental tissue was highly positive. GLUT1 mRNA could be detected in endometrial samples with an increase in endometria of the late secretory phase (day 25–28) and maximum concentration in the decidua of the 9th–10th week of gestation. Our results show that GLUT1 is differentially expressed in the different phases of the human endometrium with a maximum in the human decidua. Therefore ,GLUT1 may be an important marker for endometrial differentiation.

Expression of glucose transporter 1 in human endometrial and decidual tissue

Regulation of endometrial glucose transport is important for the decidualization process. Therefore ,we have examined the expression of the glucose transporter protein isoform 1 (GLUT1) in endometrial samplesduring the menstrual cycle and in decidual tissue by immunohistochemistry ,and GLUT1 mRNA by RNase protection assays. GLUT1 protein was not detected in proliferative endometrial samples ,but was highlyexpressed in decidual tissue. Placental tissue was highly positive. GLUT1 mRNA could be detected in endometrial samples with an increase in endometria of the late secretory phase (day 25–28) and maximumconcentration in the decidua of the 9th–10th week of gestation. Our results show that GLUT1 is differentially expressed in the different phases of the human endometrium with a maximum in the humandecidua. Therefore ,GLUT1 may be an important marker for endometrial differentiation.

The presence and role of the dopamine DA-2 receptor in the human decidua.

Our objectives were to identify the presence of the dopamine DA-2 receptor in human decidua and to study its function in human parturition. Human term decidual tissues were obtained during vaginal delivery and then homogenized. The P3 fraction was prepared for a radiolabeled receptor assay with [3H] spiperone as the ligand. Human decidual tissues obtained at cesarean section before the onset of labor were incubated in Krebs-Ringer buffer at 37 degrees C for 30 minutes in the presence of dopamine with or without (-)-sulpiride. The level of prostaglandin (PG) F in the medium was measured with a RIA kit. Differences were assessed with the Wilcoxon non-parametric test. Scatchard analysis showed a single class of binding sites having an equilibrium dissociation constant (Kd) of 2.25 +/- 0.59 nM (mean +/- SD) and a maximum binding capacity (Bmax) value of 166.5 +/- 77.7 fmol/mg protein (n = 3). Dopamine significantly increased the production of PGF. This stimulatory effect of dopamine was suppressed by (-)-sulpiride (p < 0.05; n = 7). The DA-2 receptor was demonstrated in the human decidua. Dopamine can stimulate PGF production via this receptor.

Human T cell leukemia cell death by apoptosis-inducing nucleosides from CD57(+) HLA-DR(bright) natural suppressor cell line.

Apoptosis‐inducing nucleosides (AINs) released from CD57+HLA‐DRbright natural suppressor (57.DR‐NS) cell line, derived from human decidual tissue, were isolated from 57.DR‐NS cell culture supernatant by the combination of thin‐layer chromatography (TLC) and high‐performance liquid chromatography (HPLC). Apoptotic cell death was strongly induced in human T cell leukemia Molt4 cells treated with AINs, absolutely depending on DNA strand breaks, with activation of the caspase cascade, especially caspase‐3. The administration of AINs to Molt4 tumor‐bearing severe combined immunodeficiency (SCID) mice resulted in drastic suppression of tumor growth, with a decrease of tumor size and the appearance of apoptotic signals in tumor tissue. Thus, AINs are candidates for development as anticancer agents.

Activation of Caspase-3 in Molt4 Cells by Apoptosis-Inducing Nucleosides from CD57+HLA-DRbright Natural Suppressor Cell Line

Apoptosis-inducing nucleosides (AINs), which were released and isolated from CD57+HLA-DRbright natural suppressor (57.DR-NS) cell line derived from human decidual tissue, induced apoptosis in Molt4 cells. The addition of caspase-3 inhibitor into the reaction blocked the cleavage of caspase-3 and apoptosis in Molt4 cells treated with AINs, detected by flow cytometrical or spectrofluorometrical analysis and DNA fragmentation assay. Furthermore, by means of immunoblotting, the processing of caspase-3 was shown with the appearance of their catalytically active subunits of 20 and 11 kDa during the generation of apoptosis in Molt4 cells treated with AINs. This processing of caspase-3 into active subunits was also blocked by the addition of caspase-3 inhibitor. Thus, it was definitely revealed that the activation of caspase-3 was a key feature in the caspase cascade of AINs-induced apoptosis in Molt4 cells.

Type-1 and type-2 cytokines in human decidual tissue and trophoblasts from normal and abnormal pregnancies detected by reverse transcriptase polymerase chain reaction (RT-PCR).

Cytokine expression at the maternal fetal interface has been well documented in rodents, but data in the human are scanty and controversial. We examined cytokine expression of human decidua and trophoblasts by semiquantitative visual grading of reverse transcriptase polymerase chain reaction (RT-PCR) products in five groups of patients: ten patients with uncomplicated term pregnancies undergoing elective cesarean section (Group 1); ten women having normal pregnancies at term and vaginal delivery (Group 2); ten patients having intrauterine growth-retarded infants of unknown cause after a spontaneous vaginal delivery at term (Group 3); ten childless women having their first, first-trimester spontaneous abortion (Group 4); and ten childless women with a history of one or more previous first-trimester spontaneous abortions and having a new miscarriage (Group 5). Results favoring the T-helper 1 (Th1)/T-helper 2 (Th2) model during pregnancy were: significantly higher expression of interferon gamma (IFN-gamma) in trophoblast samples from Group 3 versus 2 and in decidual tissue from Group 5 versus 4; stronger positivity of interleukin (IL)-10 in decidual tissue samples from Group 1 versus Groups 2 and 5; and higher expression levels of tumor necrosis factor-beta (TNF)-beta by the trophoblast in Group 5 versus 1. Against the Th1/Th2 paradigm were the following findings: the significantly increased expression of IFN-gamma by decidual or trophoblast samples in Groups 1 versus 2, 2 versus 3, and 1 versus 5; and the significantly higher expression of TNF-alpha in decidual samples from patients in Group 1 (but also Group 4) as compared with Group 5. IL-2 mRNA and IL-4 mRNA could not be detected. Overall, our findings suggest that there is a balance between type-1 and type-2 cytokines during pregnancy, which is mainly characterized by the expression of IFN-gamma (a type-1 cytokine) and IL-10 (a type-2 cytokine) at the maternal fetal interface.

Inhibitory effect of interleukin-8 on the secretion of platelet-activating factor acetylhydrolase by human decidual macrophages

To determine whether interleukin-8 (IL-8) regulates platelet-activating factor acetylhydrolase (PAF-AH) secretion by decidual cells in vitro. Decidual macrophages were obtained from human term decidual tissue by enzymic digestion and Ficoll-Paque centrifugation. The effect of IL-8 and phorbol esters on the secretion of PAF-acetylhydrolase by these cells was examined. IL-8 inhibited PAF-AH secretion by decidual macrophages in a dose-dependent manner. The inhibition was reversed partially by antibodies against tumor necrosis factor-alpha and IL-1 beta. IL-8-induced inhibition was blocked partially by the protein kinase C (PKC) inhibitors, sphingosine, and H-7 1-(5-isoquinoline sulfonyl)-2-methylpiperazine. A PKC activator, 12-O-tetradecanoyl phorbol 13-acetate, decreased PAF-AH secretion. IL-8 may increase the PAF concentration in the decidua via its inhibitory effect on PAF-AH secretion by decidual macrophages. IL-8-induced inhibition of enzyme secretion may have been mediated in part by PKC-dependent signal transduction.

Apoptotic cell death of human gastric tumor induced by nucleosides from CD57+HLA-DRbright natural suppressor cell line.

CD57+HLA-DRbright natural suppressor (57.DR-NS) cell line derived from human decidual tissue generated apoptosis in a human gastric carcinoma cell line (GCIY) but not in a human diploid normal cell line (WI-38). The factors released from 57.DR-NS cells were purified by thin-layer-chromatography (TLC) and separated by high performance liquid chromatography (HPLC) into six components. The physicochemical structures of the six components were determined as a series of nucleosides and their modified forms collectively termed <apoptosis inducing nucleosides (AINs)> in a previous study. They could generate apoptotic cell death of GCIY malignant target cells, but not disturb the viability of WI-38 normal target cells. The administration of AINs into GCIY tumor bearing SCID mice resulted in drastic suppression of tumor growth followed by the decrease in tumor size due to the occurrence of apoptosis in tumor tissues.

Labor-associated changes in interleukin-10 production and its regulation by immunomodulators in human choriodecidua.

Parturition is associated with increased production of proinflammatory mediators by gestational tissues. Interleukin-10 (IL-10) is an antiinflammatory cytokine produced by human chorion, decidual, and trophoblast tissues. To study the effects of immunomodulators on IL-10, IL-6, and PGE2 production by human choriodecidua before and after labor, an organ explant system was established. Tissue disks (6 mm) were excised from choriodecidual membranes obtained at term by cesarean section before labor (n=6-7) or after spontaneous vaginal delivery (n=7-8). After 24-h equilibration in medium, the tissues were treated with IL-1beta (10 ng/mL), tumor necrosis factor-alpha (100 ng/mL), lipopolysaccharide (5 microg/mL), dexamethasone (1 micromol/ L), or an appropriate vehicle control (n=3 wells/treatment) for 24 h. Media were harvested, and IL-10, IL-6, and PGE2 concentrations were determined by immunoassay. Basal choriodecidual production rates of IL-10 were significantly decreased with labor (P < 0.001), whereas PGE2 and IL-6 production rates increased. The production of all three substances was increased by IL-1beta, tumor necrosis factor-alpha, and lipopolysaccharide, but inhibited by dexamethasone. In contrast to PGE2 and IL-6, there was significantly increased responsiveness of IL-10 production to inflammatory stimuli after labor, but decreased responsiveness to the inhibitory effects of dexamethasone. These data indicate that IL-10 could play a role in modulating or promoting resolution of the inflammatory processes associated with labor at term and with intrauterine infection-associated preterm labor.