dinoprost and Chorioamnionitis

Our purpose was to determine what factors occurring after digital separation of the chorionic membranes from the lower uterine segment (membrane stripping) are involved in observed clinical changes compared with patients not so treated.. Thirty patients were randomly divided among a study population and two control groups to assess uterine contractions and microbiologic, histologic, and biochemical markers associated with parturitional events over a 7-hour time frame.. Clinically, an increased frequency of uterine contractile activity was observed among patients in the membrane-stripped group (p < 0.03). There was a significant increase in plasma 13,14-dihydro-15-keto-prostaglandin F2 alpha (p < 0.001) and endocervical phospholipase A2 activity (p < 0.04) among those who underwent membrane stripping. Blood leukocyte counts, sedimentation rates, prostaglandin E2 metabolite concentrations, and fibronectin levels revealed no significant change during the 7-hour study session.. Membrane stripping was associated with increases in phospholipase A2 activity and prostaglandin F2 alpha concentrations, indicating a possible correlation with initiation of the cascade of parturitional events.

Topics: Amnion; Cervix Uteri; Chorioamnionitis; Chorion; Dinoprost; Female; Humans; Labor, Induced; Phospholipases A; Phospholipases A2; Pregnancy; Uterine Contraction; Uterus

To determine whether an elevated amniotic fluid concentration of prostaglandin F2α (PGF2α) is associated with intra-amniotic inflammation/infection and adverse pregnancy outcomes in patients with preterm labor and intact membranes.. The retrospective cohort study included 132 patients who had singleton pregnancies with preterm labor (< 35 weeks of gestation) and intact membranes. Amniotic fluid was cultured for aerobic and anaerobic bacteria as well as for genital mycoplasmas. Intra-amniotic inflammation was defined by an elevated amniotic fluid matrix metalloproteinase-8 (MMP-8) concentration (>23 ng/mL). PGF2α was measured with a sensitive and specific immunoassay. The amniotic fluid PGF2α concentration was considered elevated when it was above the 95th percentile among pregnant women at 15-36 weeks of gestation who were not in labor (≥170 pg/mL).. (1) The prevalence of an elevated amniotic fluid PGF2α concentration was 40.2% (53/132) in patients with preterm labor and intact membranes; (2) patients with an elevated amniotic fluid PGF2α concentration had a significantly higher rate of positive amniotic fluid culture [19% (10/53) versus 5% (4/79); p = 0.019], intra-amniotic inflammation/infection [49% (26/53) versus 20% (16/79); p = 0.001], spontaneous preterm delivery, clinical and histologic chorioamnionitis, and funisitis, as well as a higher median amniotic fluid MMP-8 concentration and amniotic fluid white blood cell count and a shorter amniocentesis-to-delivery interval than those without an elevated concentration of amniotic fluid PGF2α (p < 0.05 for each); and (3) an elevated amniotic fluid PGF2α concentration was associated with a shorter amniocentesis-to-delivery interval after adjustment for the presence of intra-amniotic inflammation/infection [hazard ratio 2.1, 95% confidence interval (CI) 1.4-3.1; p = 0.001].. The concentration of PGF2α was elevated in the amniotic fluid of 40.2% of patients with preterm labor and intact membranes and is an independent risk factor for intra-amniotic inflammation/infection, impending preterm delivery, chorioamnionitis, and funisitis.

Topics: Amniocentesis; Amniotic Fluid; Bacteria; Bacterial Infections; Chorioamnionitis; Cohort Studies; Dinoprost; Extraembryonic Membranes; Female; Gestational Age; Humans; Mycoplasma; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Premature Birth; Prognosis; Retrospective Studies; Risk Factors

Does Copper Metabolism MURR1 Domain 1 (COMMD1) play a role in regulating the mediators involved in the terminal processes of human labour and delivery?. COMMD1 plays a critical role in the termination of nuclear factor-κB (NF-κB) activity and the control of pro-inflammatory and pro-labour mediators.. Inflammation and infection are the biggest aetiological factors associated with preterm birth. NF-κB drives the transcription of pro-inflammatory mediators involved in the terminal effector pathways of human labour and delivery. In non-gestational tissues, COMMD1 is a negative regulator of NF-κB-induced inflammation.. The mRNA and/or protein level of COMMD1 was assessed in myometrium (n = 8 per group) and fetal membranes (n = 8 per group) obtained from term non-labouring and labouring women at term, and fetal membranes (n = 8 per group) at preterm with and without histological chorioamnionitis. Primary human myometrial cells were used to determine the effect of pro-inflammatory mediators on COMMD1 level, and the effect of COMMD1 small interfering RNA (siRNA) on pro-labour mediators. Statistical significance was ascribed to a P < 0.05.. COMMD1 expression was significantly decreased with spontaneous term labour in myometrium; in fetal membranes with histologically confirmed chorioamnionitis and in myometrial cells treated with pro-inflammatory cytokines interleukin (IL)-1β and tumour necrosis factor (TNF)-α, the bacterial product fibroblast-stimulating lipopeptide and the viral double stranded RNA analogue polyinosinic polycytidilic acid. Loss-of-function studies revealed an increase in inflammation- and infection-induced TNF-α, IL-1α, IL-1β, IL-6, IL-8 and/or monocyte chemoattractant protein-1 mRNA abundance and/or release; and cyclo-oxygenase-2 mRNA level, release of prostaglandin (PG) F2α and mRNA level of the PGF2α receptor FP. In addition, siRNA knockdown of COMMD1 was associated with significantly increased NF-κB activation as evidenced by increased IL-1β-induced IκB-α protein degradation and NF-κB DNA binding activity.. The conclusions are based on in vitro experiments with cells isolated from myometrium. Animal models, however, will be required to establish whether COMMD1 activators can prevent spontaneous preterm birth in vivo.. The control of COMMD1 activation may provide an alternative therapeutic strategy for reducing the release of pro-labour mediators in spontaneous preterm labour.. Not applicable.. Associate Professor Martha Lappas is supported by a Career Development Fellowship from the National Health and Medical Research Council (NHMRC; grant no. 1047025). Additional funding was provided by the Medical Research Foundation for Women and Babies and the Mercy Research Foundation. The author has no conflict of interest.

Topics: Adaptor Proteins, Signal Transducing; Adult; Chorioamnionitis; Cyclooxygenase 2; Diglycerides; Dinoprost; Extraembryonic Membranes; Female; Gene Expression Regulation; Humans; Interleukin-1beta; Labor, Obstetric; Myocytes, Smooth Muscle; Myometrium; NF-kappa B; Obstetric Labor, Premature; Oligopeptides; Poly I-C; Pregnancy; Premature Birth; Primary Cell Culture; Receptors, Prostaglandin; RNA, Small Interfering; Signal Transduction; Term Birth; Tumor Necrosis Factor-alpha

Forkhead box O (FoxO) proteins function primarily as transcription factors in the nucleus where they bind to their cognate DNA targeting sequences. FoxO regulated genes include those involved in cellular stress responses, inflammation and apoptosis; all of which are involved in the processes of human labour and delivery. We have previously identified Forkhead box O4 (FoxO4) proteins in human gestational tissues; there is, however, no data is available on the role of FoxO4 in the processes of human labour and delivery. Thus the aim of this study was to determine the effect of (i) human labour, preterm chorioamnionitis and pro-inflammatory stimuli on the expression of FoxO4 in human placenta and fetal membranes; and (ii) FoxO4 knockdown by siRNA on the expression of pro-labour mediators. Quantitative RT-PCR (qRT-PCR), immunohistochemistry and/or Western blotting was used to analyse the expression of FoxO4 (n = 6 per group). Human labour and preterm chorioamnionitis significantly decreased cytoplasmic FoxO4 expression in placenta and/or choriodecidua. Knockdown of FoxO4 mRNA and protein in JEG-3 cells using siRNA was associated with decreased COX-2 mRNA expression concomitant with lower PGF(2α) secretion. However, in BeWo cells, siRNA inhibition of FoxO4 was not associated with inflammation, oxidative stress or apoptosis. In summary, human term labour and chorioamnionitis is characterised by lower FoxO4 mRNA and/or protein expression in placenta and/or choriodecidua. Although the exact role of FoxO4 in human pregnancy remains to be fully elucidated, our data demonstrate that it can regulate COX-2 expression and subsequent prostaglandin expression.

Topics: Adult; Apoptosis; Cell Cycle Proteins; Cell Line; Chorioamnionitis; Cyclooxygenase 2; Cytokines; Cytoplasm; Decidua; Dinoprost; Down-Regulation; Extraembryonic Membranes; Female; Forkhead Transcription Factors; Gene Silencing; Humans; Labor, Obstetric; Parturition; Placenta; Pregnancy; Pregnancy Proteins; RNA, Messenger; RNA, Small Interfering; Transcription Factors

Acute chorioamnionitis of infectious origin and chronic chorioamnionitis of immunological origin are two major placental lesions of spontaneous preterm birth with elevated amniotic fluid interleukin-6 and CXCL10 concentrations, respectively. The changes in the amniotic fluid proteome associated with intra-amniotic infection and acute chorioamnionitis are well defined, yet alterations unique to chronic chorioamnionitis remain to be elucidated. This study was conducted to determine those amniotic fluid proteins changing specifically in the presence of chronic chorioamnionitis. Amniotic fluid obtained from acute chorioamnionitis, chronic chorioamnionitis and gestational age-matched controls were analysed by two-dimensional (2D) difference in gel electrophoresis and MALDI-TOF analyses. The type of histological inflammation was used to define each condition in preterm labour cases (n = 125) and term not in labour cases (n = 22), and the amniotic fluid concentrations of interleukin-6, CXCL8, CXCL10 and prostaglandin F(2α) were also measured by specific immunoassays. Among preterm labour cases, 31 differentially expressed proteins were identified in chronic chorioamnionitis cases as compared to both acute chorioamnionitis and control cases. Importantly, glycodelin-A, which maintains maternal tolerance against an allogeneic fetus, was decreased in chronic chorioamnionitis, while haptoglobin was increased. We report the amniotic fluid proteome of chronic chorioamnionitis for the first time, and the findings herein strongly suggest that there is a pathophysiological association between the changes of immunomodulatory proteins in the amniotic fluid and chronic chorioamnionitis, a histological manifestation of maternal anti-fetal allograft rejection.

Topics: Acute Disease; Adolescent; Adult; Amniotic Fluid; Chemokine CXCL10; Chorioamnionitis; Chronic Disease; Cross-Sectional Studies; Dinoprost; Electrophoresis, Gel, Two-Dimensional; Extraembryonic Membranes; Female; Glycodelin; Glycoproteins; Haptoglobins; Humans; Interleukin-6; Interleukin-8; Obstetric Labor, Premature; Parity; Pregnancy; Pregnancy Proteins; Proteome; Young Adult

To determine whether amniotic fluid (AF) concentration of prostaglandins (PGs) increases in patients with intra-amniotic inflammation and/or proven AF infection in preterm PROM, and can predict impending delivery.. AF PGF2a concentrations were determined by ELISA in 140 singleton pregnancies with preterm premature rupture of membranes (PROM) (< or =35 weeks). AF was cultured for aerobic and anaerobic bacteria, and genital mycoplasmas. Intra-amniotic inflammation was defined as an elevated AF matrix metalloproteinase-8 concentration (>23 ng/ml). Results. (1) Patients with intra-amniotic inflammation and a negative AF culture had a significantly higher median AF PGF2a than those without intra-amniotic inflammation and with a negative culture (p < 0.001); (2) However, there was no difference in the median AF PGF2a between patients with intra-amniotic inflammation with a negative culture and those with culture-proven AF infection (p > 0.1); (3) Patients with an elevated AF PGF2a had a significantly shorter interval-to-delivery than those with a low AF PGF2a (< or =170 pg/mL) (p < 0.001); (4) An elevated AF PGF2a (< or =170 pg/mL) concentration was a significant predictor of the duration of pregnancy after adjusting for gestational age and AF inflammation/infection (p < 0.005). Conclusions. AF PGF2a (> or =170 pg/mL) concentration increased in patients with intra-amniotic inflammation regardless of AF culture results. Moreover, an elevated AF PGF2a concentration was an independent predictor of impending delivery in preterm PROM.

Topics: Adult; Amniocentesis; Amniotic Fluid; Bacteriological Techniques; Chorioamnionitis; Delivery, Obstetric; Dinoprost; Female; Fetal Membranes, Premature Rupture; Humans; Middle Aged; Pregnancy; Pregnancy Complications, Infectious; Prognosis; Time Factors; Up-Regulation; Young Adult

The inflammatory process is known to cause preterm delivery. Recently, a cyclooxygenase (COX)-2 inhibitor has been developed as an anti-inflammatory drug with few side-effects. We evaluated the COX-2 inhibitor, Celecoxib, for its tocolytic effects and side-effects on dams and pups using a lipopolysaccharide (LPS)-induced preterm delivery mouse model (preterm delivery rates; 95%). With administration of Celecoxib (50, 10, 1 and 0.3 mg/kg), the preterm labour rate was significantly reduced to 18, 30, 36 and 60% respectively. The prostaglandin F(2alpha)(PGF(2alpha)) and PGE(2) concentrations in murine uterine tissue 4 and 10 h after LPS treatment with Celecoxib (10 and 1 mg/kg) were significantly lower than those in the LPS-treated group without CELECOXIB: With administration of 10 or 100 mg/kg Celecoxib, the fetal ductus arteriosus was constricted significantly in preterm and near-term rats, although constriction rates in preterm rats were significantly lower than those in near-term rats. Reproductive and renal functions in offspring whose mothers were treated with LPS and Celecoxib were normal. These data demonstrate that Celecoxib could be used as a new therapy for preterm labour. However, careful attention to constriction of the fetal ductus arteriosus should be given.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Celecoxib; Chorioamnionitis; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprost; Dinoprostone; Ductus Arteriosus, Patent; Female; Interleukin-1; Interleukin-6; Isoenzymes; Lipopolysaccharides; Male; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Models, Animal; Obstetric Labor, Premature; Pregnancy; Prostaglandin-Endoperoxide Synthases; Pyrazoles; Rats; Rats, Wistar; Sulfonamides; Time Factors; Tocolysis; Tumor Necrosis Factor-alpha; Uterus

Topics: Amniotic Fluid; Chorioamnionitis; Dinoprost; Dinoprostone; Female; Humans; Pregnancy; Pregnancy Complications, Infectious; Prostaglandins E; Prostaglandins F