Nrf_2与足月胎膜早破合并绒毛膜羊膜炎的关系

目的:探讨核因子E2相关因子(Nrf_2)表达与足月胎膜早破(PROM)合并绒毛膜羊膜炎(HCA)的关系。方法:选取足月PROM患者60例,根据胎膜组织病理检查结果分成PROM合并HCA组(HCA组,21例)和未合并HCA组(对照组,39例)。采用免疫组化法、蛋白印迹法和实时荧光定量PCR法分别检测Nrf_2在胎膜组织、母血和脐血中的表达。结果:(1)HCA组胎膜组织、母血和脐血中Nrf_2mRNA表达水平分别为0.48±0.09、0.73±0.11和0.51±0.09,Nrf_2蛋白表达水平分别为0.101±0.019、0.294±0.051和0.175±0.028;HCA组中Nrf_2mRNA和蛋白表达水平均明显低于对照组,差异有统计学意义(P0.05)。(2)Nrf_2在胎膜组织羊膜层、绒毛膜层和底蜕膜层中的细胞核和细胞质均有表达。Nrf_2定位于细胞核的表达在HCA组的每一层表达均低于对照组(P0.05);两组中,Nrf_2在羊膜层、绒毛膜层和底蜕膜层中的表达水平比较,均存在显著差异,底蜕膜最低,羊膜层最高。结论:Nrf_2表达水平显著下降是PROM合并HCA的重要发病机制。Nrf_2含量变化可成为一种新的生物学标记物用于诊断PROM合并HCA的孕妇和评估新生儿预后。     

Progesterone receptor localization and isoforms in myometrium,decidua, and fetal membranes from rhesus macaques: evidence for functional progesterone withdrawal at parturition

OBJECTIVE: It is not known whether withdrawal of progesterone (P) action is a prerequisite for parturition in women or in nonhuman primates because concentrations of circulating progesterone or progesterone receptors (PR) in myometrium and decidua do not decrease before delivery. To examine this potentially important regulatory mechanism, we determined PR isoforms, PR localization, and mRNA in myometrium, decidua, and fetal membranes from rhesus monkeys during pregnancy and in spontaneous labor at term.METHODS: Gestational tissues were obtained midpregnancy (day 80-100), late pregnancy (day 130-145), and during spontaneous labor at term (day 161-167). Samples of rhesus monkey myometrium, decidua, chorion-decidua, and amnion were collected and analyzed for total nuclear and cytosolic PR by competitive binding assay. Progesterone receptor isoforms were identified and quantified by Western blot analysis, and PR mRNA was determined by a specific ribonuclease protection assay. Nuclear PR was localized by immunohistochemistry with monoclonal anti-PR (JZB39) after microwave stabilization.RESULTS: Myometrium and decidua showed no change in total PR during pregnancy and labor. Nuclear PR was not detected in fetal membranes by binding assay but was localized in amnion epithelial and mesenchymal cells and in chorion laeve cytotrophoblasts by immunohistochemistry. Staining for PR was substantially less by serial antibody dilution in fetal membranes than in decidua. Message for PR was confirmed in all tissues analyzed. A significant (P <.05) shift in the ratio of PR isoforms (from PR-B dominance at midpregnancy to PR-A dominance in labor) was observed in myometrium but not in decidua. Both PR-A and PR-B isoforms and PR nuclear staining were nearly undetectable in amnion obtained during labor.CONCLUSION: A shift to PR-A dominance in myometrium at term together with a loss of PR in fetal membranes provides evidence for a functional progesterone withdrawal mechanism, which may facilitate the initiation of parturition in primates.     

Association of type II apoptosis and 92-kDa type IV collagenase expression in human amniochorion in prematurely ruptured membranes with tumor necrosis factor receptor-1 expression

OBJECTIVE: We assessed the presence of tumor necrosis factor receptor-1 (TNF-R1), apoptosis, and simultaneous expression of 92-kDa collagenase type IV (MMP-9) in samples of human chorioamnion from women with premature rupture of membranes (PROM). METHODS: Amniotic membranes from women who underwent normal labor, cesarean delivery, or had PROM at term were studied by immunohistochemistry for localization of TNF-R1 and R2. Transmission electron microscopy and DNA fragmentation analyses by agarose gel electrophoresis were performed to identify apoptosis characteristics. Zymography and in situ zymography were used to assess gelatinolytic activity. RESULTS: We found that TNF-R1 was abundant in membranes from subjects who had normal labor and very abundant in those who had PROM. By contrast TNF-R2 was abundant only in membranes from subjects who had cesarean delivery. Gelatinolytic activity was associated with extracellular matrix rather than cells and was higher in extracts from fetal membranes from PROM and normal labor than in extracts obtained from cesarean deliveries. Transmission electron microscopy of fetal membranes from PROM revealed ultrastructural characteristics in amnion epithelium consistent with type II apoptosis. DNA laddering in agarose gel electrophoresis corroborated results from DNA fragmentation. CONCLUSION: During PROM the fetal membranes undergo type II apoptosis and extracellular matrix degradation in association with TNF-R1 expression.     

Pre-B-cell colony-enhancing factor,a novel cytokine of human fetal membranes

OBJECTIVE: Our purpose was to determine whether pre-B-cell colony-enhancing factor (PBEF) is expressed in the human fetal membranes during normal gestation and parturition in the absence of infection and to show its effects on the expression of interleukin (IL)-6 and IL-8. STUDY DESIGN: PBEF was immunolocalized in the fetal membranes from early pregnancy, at preterm, and at term. Its expression was quantitated by Northern analysis in separated uninfected amnion, chorion, decidua, and placenta of patients at term before labor and in full-thickness membranes before and after spontaneous labor at preterm and at term. Amnion-like epithelial (WISH) cells and fetal membrane explants were treated with recombinant PBEF (rhPBEF), and the expression of IL-6 and IL-8 was quantitated. RESULTS: PBEF was immunolocalized throughout gestation in the amniotic epithelium and mesenchymal cells as well as the chorionic cytotrophoblast and parietal decidua. Northern analysis showed significantly more (P <.01) PBEF expressed in the amnion than in either chorion or placenta. Its expression increased after labor at both preterm and term and correlated with that of IL-8 (r = 0.87). rhPBEF treatment of WISH cells significantly increased IL-6 (P <.05) and IL-8 (P <.01) gene expression after 4 hours and of IL-8 protein after 24 hours (P <.01); similar 4-hour treatment of fetal membrane explants significantly increased IL-6 (P <.01) and IL-8 (P <.05) gene expression. CONCLUSION: PBEF is a novel cytokine constitutively expressed by the fetal membranes during pregnancy. It increased the expression of IL-6 and IL-8 and may be important in both normal spontaneous labor and infection-induced preterm labor.     

Localization of prostaglandin H synthase, prostaglandin dehydrogenase, corticotropin releasing hormone and glucocorticoid receptor in rhesus monkey fetal membranes with labor and in the presence of infection

Prostaglandins (PGs) play a central role in primate parturition by their actions on uterine contractility and on cervical ripening. Rhesus monkey placentation is hemochorial and the endocrine events surrounding parturition are qualitatively similar to human pregnancy. Although there is an increase in PG production before the onset of labor, little is known about the cellular localization of the PGH synthase (PGHS) or the 15-hydroxy PG dehydrogenase (PGDH) in the fetal membranes of nonhuman primates and whether it changes at term in spontaneous labor or during preterm labor associated with infection. Placental corticotropin releasing hormone (CRH) and the glucocorticoid receptor (GR) have also been implicated as mediators in parturition by virtue of their roles in PG production. We utilized immunohistochemical methods to localize the inducible isoform PGHS-2, PGDH, GR and CRH in rhesus monkey amnion, chorion and attached decidua. Tissues were obtained at cesarean section during late pregnancy, in spontaneous labor at term and in premature labor induced by Group B streptococcal intraamniotic infection. Specific staining for immunoreactive (ir)-PGHS-2 was observed in amnion epithelial and mesenchymal cells and to a lesser extent in chorion and decidua. In contrast, ir-PGDH was localized primarily to the extravillous trophoblast layer of chorion. GR was localized to both the cytoplasm and nucleus of amnion epithelial cells, subepithelial fibroblasts, chorion trophoblasts and in decidua. Immunostaining for CRH was found in amnion and in scattered decidual cells but was most intense in the chorion trophoblast layer. There was no demonstrable change in this overall pattern of immunostaining in association with the onset of labor at term except for a decrease in staining for ir-PGDH in chorion. Experimental Group B streptococcal chorioamnionitis resulted in preterm labor and extensive necrosis of extravillous trophoblast cells with subsequent loss of chorionic ir-PGDH and relative sparing of ir-PGHS-2 in amnion epithelium which favors the net production of PGs. The expression pattern of these effectors in the rhesus monkey fetal membranes points to a functional role of PGs and glucocorticoids in the process of term and preterm parturition which is similar to that in human pregnancy.     

The content of placental protein 12 in decidua and fetal membranes is greater than in placenta

Summary. Radioimmunoassay, gel filtration and sodium dodecyl sulphate-polyacrylamide gel electrophoresis were used to study the content and properties of placental protein 12 (PP12) in the placenta, decidua and fetal membranes. The tissues were obtained from early pregnancy in 12 cases, and after normal term delivery in eight cases in seven of which chorion and amnion laeve were also studied. There was more PP12 in decidua and fetal membranes than in placenta. The decidua/placenta ratio of PP12 content ranged from 2 to 1154 (mean 193, SEM 66). These results suggest that PP12 is a decidual rather than placental protein.     

The content of placental protein 12 in decidua and fetal membranes is greater than in placenta

Radioimmunoassay, gel filtration and sodium dodecyl sulphate-polyacrylamide gel electrophoresis were used to study the content and properties of placental protein 12 (PP12) in the placenta, decidua and fetal membranes. The tissues were obtained from early pregnancy in 12 cases, and after normal term delivery in eight cases in seven of which chorion and amnion laeve were also studied. There was more PP12 in decidua and fetal membranes than in placenta. The decidua/placenta ratio of PP12 content ranged from 2 to 1154 (mean 193, SEM 66). These results suggest that PP12 is a decidual rather than placental protein.     

Matrix metalloproteinase 3 in parturition,premature rupture of the membranes,and microbial invasion of the amniotic cavity

OBJECTIVE: Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that are expressed in many inflammatory conditions and contribute to connective tissue breakdown. Stromelysin 1 [matrix metalloproteinase 3 (MMP-3)], a novel member of this family, is produced in the context of infection and is able to activate the latent forms of other MMPs. The purpose of this study was to determine if parturition (either term or preterm), premature rupture of the membranes (PROM), and microbial invasion of the amniotic cavity are associated with changes in amniotic fluid concentrations of MMP-3. STUDY DESIGN: A cross-sectional study was conducted, which included women who underwent transabdominal amniocentesis (n = 365) in the following categories: (1) mid-trimester with a subsequent normal pregnancy outcome (n = 84) and a subsequent fetal loss (n = 10); (2) preterm labor with intact membranes without microbial invasion of the amniotic cavity who delivered at term (n = 36), or prematurely (n = 50), and preterm labor with microbial invasion of the amniotic cavity (n = 25); (3) preterm PROM with (n = 25) and without (n = 26) microbial invasion of the amniotic cavity; (4) term with intact membranes in the absence of microbial invasion of the amniotic cavity, in labor (n = 52) and not in labor (n = 31); and (5) term with PROM in the absence of microbial invasion of the amniotic cavity and not in labor (n = 26). MMP-3 concentrations in amniotic fluid were measured by a sensitive and specific immunoassay that was validated for amniotic fluid. MMP-3 concentrations were normalized using logarithmic transformation for statistical analysis. Parametric statistics were used and a p value < 0.05 was considered statistically significant. RESULTS: (1) MMP-3 was detected in 99.5% (363/365) of amniotic fluid samples, and its concentration did not change with advancing gestational age. (2) Spontaneous parturition at term and preterm was associated with a significant increase in amniotic fluid MMP-3 concentrations (p = 0.04 and p = 0.002, respectively). (3) Spontaneous rupture of membranes in term and preterm gestations was not associated with significant changes in amniotic fluid MMP-3 concentrations. (4) Intra-amniotic infection was associated with a significant increase in amniotic fluid MMP-3 concentrations in both women with preterm labor and intact membranes (p = 0.03), and women with preterm PROM (p = 0.02). (5) Subsequent fetal loss after genetic amniocentesis was not associated with significant changes in mid-trimester concentrations of amniotic fluid MMP-3. CONCLUSIONS: (1) MMP-3 is a physiologic constituent of amniotic fluid. (2) MMP-3 may play a role in the mechanisms of human parturition and in the regulation of the host response to intrauterine infection.     

Steroid synthetic and prostaglandin metabolizing activity is present in different cell populations from human fetal membranes and decidua

We examined whether different cell subpopulations from human fetal membranes and decidua produce steroids (estrone and progesterone) and metabolize prostaglandins (prostaglandin F2 alpha to 13, 14-dihydro-15-keto-prostaglandin F2 alpha and if these changed with labor. Amnion, chorion, and decidua were obtained at elective cesarean section at term or at spontaneous labor. Cells were dispersed with collagenase and separated by density on discontinuous Percoll gradients. At cesarean section there was a major broad band of cells from amnion and chorion. This band contained most of the estrone sulfatase (estrone sulfate to estrone) activity. The 3 beta-hydroxysteroid dehydrogenase (pregnenolone to progesterone conversion) and prostaglandin F2 alpha metabolizing activities were present in these cells and those that migrated at greater Percoll densities. Amnion and chorion obtained after spontaneous labor had two major bands of cells. Estrone sulfatase was present in cells from both hands, whereas progesterone output from pregnenolone and prostaglandin F2 alpha metabolism predominated in the second band of cells with greater density. This pattern was particularly apparent in chorion. Dispersed cells from decidua tended to migrate throughout the gradient. In general, estrone sulfate to estrone conversion predominated in lighter cells whereas progesterone output from pregnenolone and prostaglandin F2 alpha metabolism predominated in cells of greater density. The output of progesterone from pregnenolone was significantly lower in cell preparations from chorion and decidua at spontaneous labor compared with cesarean section. We conclude that human amnion, chorion, and decidua contain distinct cell subpopulations based on Percoll migration and that in the membranes these change between cesarean section and spontaneous labor. Partial separation of estrone sulfatase from 3 beta-hydroxysteroid dehydrogenase and prostaglandin F2 alpha metabolizing activities has been demonstrated, which raises the possibility of paracrine interactions in vivo.     

基质金属蛋白酶2、9及其特异性组织抑制剂在自发性胎膜早破发病中的作用

目的　探讨基质金属蛋白酶 (MMP) 2、9及其特异性组织抑制剂 (TIMP)在自发性胎膜早破发病中的作用。方法　采用RT PCR方法对 8例自发性胎膜早破患者 (胎膜早破组 )、8例正常阴道分娩产妇 (阴道分娩组 )以及 8例择期剖宫产产妇 (剖宫产组 )的胎膜组织中MMP 2、MMP 9和TIMP 2、TIMP 1mRNA的表达进行检测。结果　 (1)MMP 2 :胎膜早破组为 0 84 9± 0 0 37,阴道分娩组为 0 32 7± 0 0 2 3,剖宫产组为 0 30 7± 0 0 2 8。胎膜早破组MMP 2表达水平明显高于阴道分娩组和剖宫产组 ,两组比较 ,差异有统计学意义 (P <0 0 5 ) ;阴道分娩组MMP 2表达水平与剖宫产组比较 ,差异均无统计学意义 (P >0 0 5 )。 (2 )MMP 9:胎膜早破组为 0 0 2 6± 0 0 0 4 ,阴道分娩组为 0 0 0 8± 0 0 0 1,剖宫产组无表达。胎膜早破组MMP 9表达水平明显高于阴道分娩组 ,两者比较 ,差异有统计学意义 (P <0 0 5 )。 (3)TIMP 2 :胎膜早破组为 0 4 2 0± 0 12 2 ,阴道分娩组为 0 730± 0 14 8,剖宫产组为 0 885± 0 0 6 5。胎膜早破组TIMP 2表达水平明显低于阴道分娩组和剖宫产组 ,两者比较 ,差异有统计学意义 (P <0 0 5 ) ;阴道分娩组TIMP 2表达水平明显低于剖宫产组 ,两组比较 ,差异有统计学意义 (P <0 0 5 )。 (4)TI     

Substrate utilization for estrogen synthesis by human fetal membranes and decidua

We have investigated the ability of tissue explants of human amnion, chorion, and decidua to produce estrone when incubated alone or in the presence of estrone sulfate, dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, or testosterone. Amnion produced very little estrone from any substrate. Chorion utilized all substrates and decidua utilized estrone sulfate and dehydroepiandrosterone sulfate for estrone production. For both chorion and decidua, estrone sulfate was quantitatively the most important substrate. Chorionic tissues obtained after spontaneous labor produced greater levels of estrone than tissues obtained before labor (p less than 0.05). We could demonstrate no effect of cortisol, estriol, progesterone, prostaglandins, oxytocin, or dibutyryl cyclic adenosine monophosphate on estrogen production. We also measured endogenous concentrations of estrone and estradiol in fetal membranes. We found no significant difference in tissue concentrations between the two methods of delivery. There was no significant correlation between estrone and estradiol concentrations and distance from the placenta. We conclude that human chorion and decidua can produce estrogen, which may have some role in determining the timing of parturition.     

15-Hydroxyprostaglandin dehydrogenase protein expression in human fetal membranes with and without subclinical inflammation

Prostaglandins play a central role in the stimulation and maintenance of both term and preterm labor. 15-Hydroxyprostaglandin dehydrogenase (PGDH), localized primarily to chorion trophoblasts, is the key enzyme responsible for the metabolism of prostaglandins. In preterm chorion, levels of PGDH protein and activity were lower when compared to term and were further reduced with the presence of infection, but effects of subclinical inflammation and membrane rupture on PGDH expression are not known. Our objectives were (1) to determine the relative expression of PGDH in amnion and chorion and (2) to determine the effect of preterm premature rupture of membranes (PPROM) and (3) subclinical inflammation on PGDH protein expression in preterm fetal membranes. Fetal membranes were collected from women with idiopathic preterm labor. Patients were divided into preterm birth (1) <32 weeks with PPROM (n = 6), (2) <32 weeks with intact membranes (n = 11), (3) >or=32 and <37 weeks with PPROM (n = 10), and (4) >or=32 and <37 weeks with intact membranes (n = 10). Different antibodies were used to detect protein expression and localization of PGDH in amnion and chorion from these patients using both Western blotting and immunohistochemistry. Antibody T (AbT) localized PGDH to chorion trophoblasts, whereas antibody C (AbC) detected immunoreactive (ir) PGDH predominantly in the amnion mesenchyme. By Western blot, AbT showed a stronger 29-kDa ir-PGDH band whereas with AbC, a stronger 55-kDa ir-PGDH signal was detected. 55-kDa ir-PGDH was significantly higher in PPROM amnion, specifically in the <32 weeks group (P < .05) and with PPROM >24 hours (P < .05). No change was detected in the 29-kDa ir-PGDH in either amnion or chorion with gestational age or the presence and absence of PPROM. In addition, neither form of ir-PGDH was altered significantly with or without subclinical inflammation. ir-PGDH is detectable in both chorion trophoblasts and amnion, especially in the mesenchyme; however, the predominant form of the enzyme differs in the 2 tissues. PPROM and subclinical inflammation do not appear to affect the levels of 29-kDa ir-PGDH protein in the fetal membranes. The differential expression of 55-kDa ir-PGDH in preterm amnion with and without PPROM supports the need for a better understanding of the different forms of PGDH.     

The human relaxin receptor (LGR7): expression in the fetal membranes and placenta

The relaxin receptor has been recently described as a leucine-rich repeat G-protein coupled receptor and designated as LGR7. A closely related receptor, LGR8, is co-expressed by some cells. This study explored the expression of the genes for these receptors in the human fetal membranes and placenta by RT-PCR and the LGR7 protein by immunolocalization. The results showed that LGR7 was well expressed in the fetal membranes, with significantly more in the decidua (p<0.05) than in the amnion. On the other hand, relatively low levels were expressed in the placenta. The major splice variant of LGR7 was undetectable in either the placenta or fetal membranes. Expression of LGR8 was also below the level of detectability in either tissue. Immunostaining for LGR7 was conducted with antisera to both its endodomain and ectodomain, in order to seek evidence for a solubilized ectodomain. However, similar staining patterns were obtained with both antisera, with predominant staining in the cells of the amniotic epithelium, chorionic cytotrophoblast and decidua. Full-thickness fetal membranes from preterm deliveries, before and after labor or after preterm premature rupture of the membrane (PPROM) and labor were collected. In addition, membranes at term, both before and after spontaneous labor were used for analysis of LGR7 gene expression. There was significantly greater LGR7 expressed (p=0.01) in the preterm period compared to term, indicating a potentially important role for relaxin at this time. There was a marginal decline in LGR7 gene expression after labor and delivery both at preterm and term, which did not reach significance. Immunostaining patterns showed less inter-patient variability than did gene expression, with more intense staining for LGR7 after labor and delivery.     

Localization of the Fas-Fas ligand system in human fetal membranes

OBJECTIVE: To determine if fetal membranes might be one of the sources of Fas and Fas ligand in amniotic fluid. STUDY DESIGN: Human fetal membranes from elective cesarean section (n = 6) were fixed in paraformaldehyde. Rolls of paraffinembedded fetal membranes were cut into 5-micron sections. After blocking with horse and goat sera, sections were incubated overnight with primary antibodies followed by the appropriate secondary antibodies. Avidin-biotin complex and diaminobenzidine were used for immunoperoxidase localization. Expression of Fas and Fas ligand was read by light microscopy. RESULTS: Both Fas and Fas ligand were localized in amnion, chorion and decidual layers. In amnion, Fas and Fas ligand were expressed predominantly in epithelial cells and fibroblasts, while there was no immunostaining in the subepithelial compact connective tissue. In the chorion, the expression was mainly in the chorionic trophoblast, with inconsistent expression in the reticular layer. In the decidua, the expression of Fas and Fas ligand was less prominent than in amnion and chorion. CONCLUSION: Localization of Fas and Fas ligand in human fetal membranes suggests that fetal membranes could be one of the sources of soluble Fas and Fas ligand in amniotic fluid.     

Endothelin transfer and endothelin effects on water transfer in human fetal membranes.

Although endothelin-1 is synthesized by human amnion, its physiologic role and its ability to be transferred to myometrium for oxytocic action remain unclear. We investigated the transfer of endothelin-1 itself and the effects of endothelin-1 on the transfer of tritiated water across human amnion or amnion/chorion/decidua in vitro with an Ussing chamber technique. Permeability coefficients (mean +/- standard error) for 3H2O across amnion/chorion/decidua in the fetal to maternal direction were 1.26 +/- 0.21 and 1.25 +/- 0.10 x 10(-4) cm/second (N = 6) and in the maternal to fetal direction 0.90 +/- 0.07 and 0.98 +/- 0.15 x 10(-4) cm/second (N = 5) in the absence or presence, respectively, of 10(-9) mol/L endothelin-1 in the fetal reservoir. Comparable values were found in either direction with 10(-9) mol/L endothelin-1 in the maternal reservoir. Apparent permeability coefficients for 125I endothelin-1 in the fetal to maternal direction were 3.34 +/- 0.79 and 2.43 +/- 0.68 x 10(-5) cm/second (N = 5) for amnion or amnion/chorion/decidua. However, appreciable trapping of 125I endothelin-1 by the fetal membranes was apparent. Endothelin-1 does not appear to affect water movement across the human fetal membranes, and only a small proportion of endothelin-1 itself is transferred across the membranes.     

Changes in prostaglandin transfer across human fetal membranes obtained after spontaneous labor

Increased prostaglandin E2 production from amnion is thought to be a critical step in the initiation of human parturition. However, it is not known whether amniotic prostaglandin E2 can reach the decidua and/or myometrium. We examined whether prostaglandin E2 could cross the amnion and full-thickness membranes and whether this capacity changed with active labor. Using an in vitro system we found that there was a time-dependent cumulative transfer of total radioactivity and of radioactivity corresponding chromatographically to prostaglandin E2 across amnion and full-thickness membranes. The rate of transfer across the amnion was faster than across full-thickness membranes and varied according to the site of tissue sampling within the uterus. The permeability constant for prostaglandin E2 transfer across full-thickness membranes was significantly higher in tissue collected after the spontaneous onset of labor than in tissue collected at elective cesarean section at term. We conclude that prostaglandin E2 produced in human amnion at term may escape metabolism in the chorion and reach the decidua and/or myometrium.     

Changes in expression of the cyclooxygenase gene in human fetal membranes and placenta with labor.

OBJECTIVE: Our objective was to examine the expression of the gene coding for cyclooxygenase, the central enzyme in prostaglandin synthesis, in human placenta and fetal membranes during pregnancy and before and after labor at term. STUDY DESIGN: Expression of the gene for cyclooxygenase was examined with Northern hybridization to ribonucleic acid from human placenta throughout pregnancy and human amnion and chorion decidua in the late third trimester. RESULTS: Expression was undetectable in trophoblast during the first and second trimesters. Expression in amnion and trophoblast increased 3.5- and 2.5-fold, respectively, in association with labor. CONCLUSIONS: Our results suggest that the increase in prostaglandin synthesis within the uterus that is seen with the onset of labor is associated with an increase in the expression of the gene cyclooxygenase.