dinoprost and Premature-Birth

Preterm birth is the leading cause of infant morbidity and mortality worldwide. Elevated levels of oxidative stress have been associated with an increased risk of delivering before term. However, most studies testing this hypothesis have been conducted in racially and demographically homogenous study populations, which do not reflect the diversity within the United States.. We leveraged 4 cohorts participating in the Environmental Influences on Child Health Outcomes Program to conduct the largest study to date examining biomarkers of oxidative stress and preterm birth (N=1916). Furthermore, we hypothesized that elevated oxidative stress would be associated with higher odds of preterm birth, particularly preterm birth of spontaneous origin.. This study was a pooled analysis and meta-analysis of 4 birth cohorts spanning multiple geographic regions in the mainland United States and Puerto Rico (208 preterm births and 1708 full-term births). Of note, 8-iso-prostaglandin-F. Approximately 11% of our analytical sample was born before term. Relative to full-term births, an interquartile range increase in averaged concentrations of F. Here, oxidative stress, as measured by 8-iso-prostaglandin-F

Topics: Biomarkers; Child; Dinoprost; Female; Humans; Infant, Newborn; Outcome Assessment, Health Care; Oxidative Stress; Pregnancy; Premature Birth; United States

Increased cortisol release in parturient cows may either represent a stress response or is part of the endocrine changes that initiate calving. Acute stress elicits an increase in heart rate and decrease in heart rate variability (HRV). Therefore, we analyzed cortisol concentration, heart rate and HRV variables standard deviation of beat-to-beat interval (SDRR) and root mean square of successive beat-to-beat intervals (RMSSD) in dairy cows allowed to calve spontaneously (SPON, n = 6) or with PGF2α-induced preterm parturition (PG, n = 6). We hypothesized that calving is a stressor, but induced parturition is less stressful than term calving. Saliva collection for cortisol analysis and electrocardiogram recordings for heart rate and HRV analysis were performed from 32 hours before to 18.3 ± 0.7 hours after delivery. Cortisol concentration increased in SPON and PG cows, peaked 15 minutes after delivery (P < 0.001) but was higher in SPON versus PG cows (P < 0.001) during and within 2 hours after calving. Heart rate peaked during the expulsive phase of labor and was higher in SPON than in PG cows (time × group P < 0.01). The standard deviation of beat-to-beat interval and RMSSD peaked at the end of the expulsive phase of labor (P < 0.001), indicating high vagal activity. Standard deviation of beat-to-beat interval (P < 0.01) and RMSSD (P < 0.05) were higher in SPON versus PG cows. Based on physiological stress parameters, calving is perceived as stressful but expulsion of the calf is associated with a transiently increased vagal tone which may enhance uterine contractility.

Topics: Adrenal Glands; Animals; Birth Weight; Cattle; Dairying; Dinoprost; Female; Heart Rate; Homeostasis; Hydrocortisone; Labor, Induced; Parturition; Pregnancy; Premature Birth; Saliva; Stress, Physiological; Sympathetic Nervous System

Preterm delivery (PTD) occurs before the 37th week of gestation. Iron deficiency anemia and inflammatory processes either related to infection or sterile inflammatory response represent risk factors for PTD. Bovine lactoferrin (bLf), an emerging important regulator of iron and inflammatory homeostasis, can represent a new therapeutic approach for PTD treatment. Here an open-label cohort and subcohort study is reported. The cohort was designed to assess the effect of bLf oral administration on iron and inflammatory homeostasis in anemic pregnant women. The subcohort including women of the cohort with PTD threat was additionally treated with bLf intravaginal administration. A significant improvement of hematological parameters was observed in the women's cohort together with a consistent decrease of serum interleukin-6 (IL-6) levels. Combined administration of oral and intravaginal bLf to the women's subcohort with PTD threat decreased IL-6 in both serum and cervicovaginal fluids, cervicovaginal prostaglandin F(2α), and suppressed uterine contractility. BLf administration blocked further shortening of cervical length and the increase of fetal fibronectin thus prolonging the length of pregnancy. The deliveries occurred between the 37th and 38th week of gestation. These results provide strong evidence for a role of bLf in PTD treatment, thus extending the therapeutic potential of this multifunctional natural protein.

Topics: Administration, Intravaginal; Administration, Oral; Anemia, Iron-Deficiency; Animals; Cattle; Cervix Uteri; Dinoprost; Female; Humans; Immunologic Factors; Interleukin-6; Lactoferrin; Pregnancy; Pregnancy Complications; Premature Birth; Risk Factors; Treatment Outcome; Uterine Cervicitis

In pursuit of more effective-labor delaying tocolytic agents, the prostaglandin F2α (PGF2α) receptor (FP) modulator PDC113.824 [(6S)-2] represents a potent lead for developing therapy to treat preterm birth. Derivatives of FP modulator (6S)-2 were synthesized, possessing respectively 5- and 7-hydroxyl groups on the indolizidin-2-one amino acid (I

Topics: Dinoprost; Female; Humans; Infant, Newborn; Myometrium; Premature Birth; Tocolytic Agents; Uterine Contraction

Preterm birth is one of the major causes of neonatal morbidity and mortality across the world. Both term and preterm labour are preceded by inflammatory activation in uterine tissues. This includes increased leukocyte infiltration, and subsequent increase in chemokine and cytokine levels, activation of pro-inflammatory transcription factors as NF-κB and increased prostaglandin synthesis. Prostaglandin F2α (PGF2α) is one of the myometrial activators and stimulators.. Here we investigated the role of PGF2α in pro-inflammatory signalling pathways in human myometrial cells isolated from term non-labouring uterine tissue. Primary myometrial cells were treated with G protein inhibitors, calcium chelators and/or PGF2α. Nuclear extracts were analysed by TranSignal cAMP/Calcium Protein/DNA Array. Whole cell protein lysates were analysed by Western blotting. mRNA levels of target genes were analysed by RT-PCR.. The results show that PGF2α increases inflammation in myometrial cells through increased activation of NF-κB and MAP kinases and increased expression of COX-2. PGF2α was found to activate several calcium/cAMP-dependent transcription factors, such as CREB and C/EBP-β. mRNA levels of NF-κB-regulated cytokines and chemokines were also elevated with PGF2α stimulation. We have shown that the increase in PGF2α-mediated COX-2 expression in myometrial cells requires coupling of the FP receptor to both Gαq and Gαi proteins. Additionally, PGF2α-induced calcium response was also mediated through Gαq and Gαi coupling.. In summary, our findings suggest that PGF2α-induced inflammation in myometrial cells involves activation of several transcription factors - NF-κB, MAP kinases, CREB and C/EBP-β. Our results indicate that the FP receptor signals via Gαq and Gαi coupling in myometrium. This work provides insight into PGF2α pro-inflammatory signalling in term myometrium prior to the onset of labour and suggests that PGF2α signalling pathways could be a potential target for management of preterm labour.

Topics: Calcium; Cyclooxygenase 2; Cytokines; Dinoprost; Female; Humans; Infant, Newborn; Inflammation; Myometrium; NF-kappa B; Obstetric Labor, Premature; Premature Birth; RNA, Messenger

Preterm birth (PTB; gestational age <37 weeks), the leading cause of infant morbidity and mortality worldwide, is of particular concern in Puerto Rico. Rates of PTB in Puerto Rico peaked at 20% in 2006, which are historically some of the highest in the world. Oxidative stress and inflammation have been implicated as contributors to adverse birth outcomes, including PTB, and these associations have not been explored in Puerto Rico. Our objective was to examine associations between urinary oxidative stress biomarkers and PTB in the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) pregnancy cohort (N = 469).. 8-iso-prostaglandin F. Averaged levels of 8-iso-PGF. Our results suggest that oxidative stress and inflammation, as measured by these biomarkers, may be important contributors to PTB. Further research is needed to improve our understanding of the role these biomarkers may play in the causal pathway between environmental factors and PTB.

Topics: Biomarkers; Dinoprost; Female; Gestational Age; Humans; Infant; Infant, Newborn; Oxidative Stress; Pregnancy; Premature Birth; Puerto Rico

Oxidative stress has been implicated in numerous birth outcomes, including spontaneous preterm birth. However, the relationship with presentation at delivery has been less well studied. We assessed the relationship between oxidative stress biomarkers and gestational duration with a focus on spontaneous presentation for delivery.. Our sample included 740 women from a multi-center prospective cohort study, recruited from 2010 to 2012. Resultant measures of oxidative stress in pregnancy prostaglandin F. The 8-iso-PGF. Our data suggest that increased oxidative stress, as indicated by the 8-iso-PGF

Topics: Adult; Biomarkers; Dinoprost; Female; Humans; Infant, Newborn; Lipid Peroxidation; Oxidative Stress; Pregnancy; Pregnancy Trimester, Third; Premature Birth

To determine whether antenatal depression is associated with oxidative stress and inflammation, and secondarily, whether the association between antenatal depression and spontaneous preterm birth (SPTB) is mediated by these biomarkers.. The primary outcome included urine oxidative stress biomarkers 8-hydroxydeoxyguanosine (8-OHdG) and 8-isoprostane and plasma inflammatory biomarkers measured at 10, 18, and 26 weeks and averaged within individual. Linear and logistic regression models were used, adjusting for age, race, parity, and pre-pregnancy body mass index.. Among 462 women, 8-isoprostane was higher among depressed women (geometric mean: 299.96 pg/mL vs. 237.01 pg/mL; p = 0.001). In multivariable analyses, antenatal depression was significantly associated with an increase in average 8-isoprostane (β: 0.25; 95% CI: 0.05-0.44; p = 0.01). The association of antenatal depression with SPTB was partially mediated by 8-isoprostane. Antenatal depression was not associated with 8-OHdG or inflammatory biomarkers.. Antenatal depression was associated with higher oxidative stress across pregnancy, namely 8-isoprostane, and may impact SPTB via oxidative stress.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Case-Control Studies; Cytokines; Depression; Dinoprost; Female; Humans; Inflammation; Oxidative Stress; Pregnancy; Pregnancy Complications; Premature Birth; Regression Analysis; Young Adult

Preterm birth is the most prominent complication attributing to poor pregnancy and neonatal outcome. Infection is most commonly implicated in preterm birth; it initiates a cascade of inflammatory events that leads to the rupture of fetal membranes and spontaneous uterine contractions. Anti-inflammatory agents may thus be a therapeutic approach to prevent the premature rupture of fetal membranes and block contractions. In non-gestational tissues, the polyphenol honokiol has been shown to possess potent anti-inflammatory properties.. The aim of this study was to investigate the effect of honokiol on pro-inflammatory mediators in human gestational tissues.. Fetal membranes, myometrium and freshly isolated amnion cells and primary myometrial cells were treated with honokiol in the absence or presence of the products lipopolysaccharide (LPS) and fibroblast-stimulating lipopeptide-1 (fsl-1), the viral dsRNA analogue polyinosinic:polycytidylic acid (poly(I:C)) or the pro-inflammatory cytokines TNF or IL1B. A luciferase assay was used to determine the effect of honokiol on nuclear factor kappa B (NF-κB) RelA transcriptional activity.. Honokiol significantly decreased pro-inflammatory cytokine (IL1A, IL6) and chemokine (CXCL8, CXCL1, CCL2) mRNA expression and secretion from fetal membranes (amnion and choriodecidua) and myometrium stimulated with LPS, fsl-1 or poly(I:C). In amnion cells, honokiol also significantly decreased the expression and secretion of the extracellular matrix degrading enzyme MMP9. Moreover, in myometrium, honokiol significantly suppressed the expression of the contraction associated protein PTGFR, the secretion of the uterotonic prostaglandins PGE. Honokiol reduced the expression of pro-inflammatory and pro-labour mediators in human amnion, choriodecidua and myometrium and that this may be facilitated through the suppression of NF-κB activation. These results indicate that the polyphenol honokiol may be a potent therapeutic for the prevention of preterm birth.

Topics: Anti-Inflammatory Agents; Biphenyl Compounds; Chemokine CCL2; Chemokine CXCL1; Dinoprost; Dinoprostone; Extraembryonic Membranes; Female; Humans; Interleukin-1beta; Interleukin-8; Lignans; Myometrium; Pregnancy; Premature Birth; Primary Cell Culture; Transcription Factor RelA; Tumor Necrosis Factor-alpha

Preterm birth remains the primary cause of early neonatal death and is a major determinant for long-term health consequences. Aberrant intrauterine inflammation and infection are known to augment the synthesis of proinflammatory cytokines and induce uterine contractions, which can subsequently lead to preterm birth. The transforming growth factor-

Topics: Chemokine CCL2; Cyclooxygenase 2; Cytokines; Dinoprost; Female; Humans; Intercellular Adhesion Molecule-1; Interleukin-1beta; Interleukin-6; Interleukin-8; Myometrium; Pregnancy; Premature Birth; Smad3 Protein

Does A20 regulate mediators involved in the terminal processes of human labour in primary myometrial and amnion cells?. A20 is a nuclear factor-kappa B (NF-κB) responsive gene that acts as a negative regulator of NF-κB-induced expression of pro-labour mediators.. Inflammation is commonly implicated in spontaneous preterm birth and the processes involved in rupture of foetal membranes and uterine contractions. In myometrium and foetal membranes, the pro-inflammatory transcription factor NF-κB regulates the transcription of pro-labour mediators in response to inflammatory stimuli. In non-gestational tissues, A20 is widely recognised as an anti-inflammatory protein that inhibits inflammation-induced NF-κB signalling.. Primary human amnion and myometrial cells were used to determine the effect of pro-inflammatory mediators on A20 expression and the effect of A20 siRNA on the expression and secretion of pro-labour mediators. The expression of A20 was assessed in myometrium and foetal membranes from non-labouring and labouring women at preterm and or term (n = 8 or nine samples per group).. The effects of pro-inflammatory mediators and of A20 siRNA in cell cultures were determined by quantitative RT-PCR (qRT-PCR), western blots, immunoassays, gelatin zymography and luciferase assays. A20 expression in tissue samples was assessed by qRT-PCR. Statistical significance was ascribed to a P value < 0.05.. In primary cells isolated from myometrium and or amnion, the pro-inflammatory cytokines IL1B and TNF, the bacterial products flagellin and fsl-1, and the viral double stranded RNA analogue poly(I:C) significantly increased A20 mRNA expression via NF-κB. A20 siRNA studies in primary myometrial and amnion cells demonstrated an augmentation of inflammation-induced expression and or secretion of pro-inflammatory cytokines (IL1A, IL6), chemokines (CXCL1, CXCL8, CCL2), adhesion molecules (ICAM1, VCAM1), contraction-associated proteins (PTGS2, PTGFR, PGF2α) and the extracellular matrix degrading enzyme MMP9, as well as NF-κB activation. Inhibition of NF-κB activity significant attenuated inflammation-induced expression of pro-labour mediators in A20 siRNA transfected cells. Finally, A20 mRNA expression was decreased in myometrium and foetal membranes with labour, and in foetal membranes with chorioamnionitis.. Not applicable.. The conclusions of this study are solely reliant on the data from in vitro experiments using cells isolated from myometrium and amnion.. The results of this study raise the possibility that targeting A20 may be a therapeutic approach to reduce inflammation associated with spontaneous preterm birth.. Associate Professor Martha Lappas is supported by a Career Development Fellowship from the National Health and Medical Research Council (NHMRC; grant no. 1047025). Funding for this study was provided by the NHMRC (grant no. 1058786), Norman Beischer Medical Research Foundation and the Mercy Research Foundation. There are no competing interests.

Topics: Amnion; Chemokine CCL2; Chemokine CXCL1; Cyclooxygenase 2; Dinoprost; Female; Flagellin; Gene Expression Regulation, Developmental; Humans; Intercellular Adhesion Molecule-1; Interleukin-1alpha; Interleukin-1beta; Interleukin-6; Interleukin-8; Labor, Obstetric; Matrix Metalloproteinase 9; Myometrium; NF-kappa B; Poly I-C; Pregnancy; Premature Birth; Primary Cell Culture; Receptors, Prostaglandin; RNA, Small Interfering; Signal Transduction; Term Birth; Tumor Necrosis Factor alpha-Induced Protein 3; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

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

The purpose of this study was to investigate oxidative stress as a mechanism of preterm birth in human subjects; we examined associations between urinary biomarkers of oxidative stress that were measured at multiple time points during pregnancy and preterm birth.. This nested case-control study included 130 mothers who delivered preterm and 352 mothers who delivered term who were originally recruited as part of an ongoing prospective birth cohort at Brigham and Women's Hospital. Two biomarkers that included 8-hydroxydeoxyguanosine (8-OHdG) and 8-isoprostane were measured in urine samples that were collected at up to 4 time points (median 10, 18, 26, and 35 weeks) during gestation.. Urinary concentrations of 8-isoprostane and 8-OHdG decreased and increased, respectively, as pregnancy progressed. Average levels of 8-isoprostane across pregnancy were associated with increased odds of spontaneous preterm birth (adjusted odds ratio, 6.25; 95% confidence interval, 2.86-13.7), and associations were strongest with levels measured later in pregnancy. Average levels of 8-OHdG were protective against overall preterm birth (adjusted odds ratio, 0.19; 95% confidence interval, 0.10-0.34), and there were no apparent differences in the protective effect in cases of spontaneous preterm birth compared with cases of placental origin. Odds ratios for overall preterm birth were more protective in association with urinary 8-OHdG concentrations that were measured early in pregnancy.. Maternal oxidative stress may be an important contributor to preterm birth, regardless of subtype and timing of exposure during pregnancy. The 2 biomarkers that were measured in the present study had opposite associations with preterm birth; an improved understanding of what each represents may help to identify more precisely important mechanisms in the pathway to preterm birth.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Case-Control Studies; Deoxyguanosine; Dinoprost; Female; Humans; Infant, Newborn; Longitudinal Studies; Male; Odds Ratio; Oxidative Stress; Pregnancy; Premature Birth; Prospective Studies

Phthalate exposure occurs readily in the environment and has been associated with an array of health end points, including adverse birth outcomes. Some of these may be mediated by oxidative stress, a proposed mechanism for phthalate action.. In the present study, we explored the associations between phthalate metabolites and biomarkers of oxidative stress measured in urine samples from multiple time points during pregnancy.. Women were participants in a nested case-control study of preterm birth (n = 130 cases, n = 352 controls). Each was recruited early in pregnancy and followed until delivery, providing urine samples at up to four visits. Nine phthalate metabolites were measured to assess exposure, and 8-hydroxydeoxyguanosine and 8-isoprostane were also measured in urine as markers of oxidative stress. Associations were assessed using linear mixed models to account for intraindividual correlation, with inverse selection probability weightings based on case status to allow for greater generalizability.. Interquartile range increases in phthalate metabolites were associated with significantly higher concentrations of both biomarkers. Estimated differences were greater in association with monobenzyl phthalate (MBzP), mono-n-butyl phthalate (MBP), and monoisobutyl phthalate (MiBP), compared with di(2-ethylhexyl) phthalate (DEHP) metabolites.. Urinary phthalate metabolites were associated with increased oxidative stress biomarkers in our study population of pregnant women. These relationships may be particularly relevant to the study of birth outcomes linked to phthalate exposure. Although replication is necessary in other populations, these results may also be of great importance for a range of other health outcomes associated with phthalates.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Case-Control Studies; Deoxyguanosine; Dinoprost; Environmental Pollutants; Female; Humans; Linear Models; Oxidative Stress; Phthalic Acids; Pregnancy; Premature Birth

Elevated inflammation is a known risk factor in the pathogenesis of PTB. Despite intensive research, the etiology of idiopathic PTB is still unknown. The present study was designed to explore associations of blood concentrations of organochlorine pesticides (OCPs) with inflammatory/antioxidant gene expression, and cytokines and prostaglandin levels in PTB cases. Significantly high levels of α, β-hexachlorocyclohexane (α, β-HCH), dichlorodiphenyldichloroethane (o'p'-DDD), dichlorodiphenyldichloroethylene (p'p'-DDE), increased expression of cyclooxygenase-2 (COX-2), and decreased expression of manganese superoxide dismutase (Mn-SOD) and catalase (CAT) genes were seen in PTB cases. Also, increased protein levels of interleukin-6 (IL-6) and decreased protein levels of interleukin-4 (IL-4) and prostaglandin F2α (PGF2α) were found in maternal blood of PTB cases as compared to term controls. Elevated levels of β-HCH along with high expression of COX-2 gene or low expression of Mn-SOD or CAT genes were associated with the decrease in the period of gestation (POG).

Topics: Catalase; Cyclooxygenase 2; Cytokines; Dinoprost; Female; Gene Expression; Humans; Hydrocarbons, Chlorinated; Pesticides; Pregnancy; Premature Birth; Superoxide Dismutase

Spontaneous preterm birth is usually associated with infection, inflammation or both. Forkhead box (FOX) M1 (FOXM1), a member of the FOX family of transcription factors, has been associated with inflammation. The aim of this study was to determine whether FOXM1 regulates the expression and release of pro-labour mediators in human gestational tissues. FOXM1 mRNA and protein expression were determined in fetal membranes from women at (1) preterm no labour: Caesarean section with no labour and (2) preterm labour: after spontaneous labour and delivery. Primary amnion cells were utilised to investigate the effect of small interfering RNA (siRNA)-mediated gene silencing of FOXM1 on pro-labour mediators. Spontaneous preterm labour decreased FOXM1 gene and nuclear protein expression. FOXM1 silencing in primary amnion cells increased interleukin (IL)-1β-induced pro-inflammatory cytokines (IL-6 and IL-8 mRNA expression and secretion), cyclooxygenase (COX)-2 expression and subsequent prostaglandin (PG)E2 and PGF2α release as well as gene expression and secretion of the matrix-degrading enzyme matrix metalloproteinase 9 (MMP-9). In conclusion, spontaneous preterm labour is associated with decreased FOXM1 expression in fetal membranes.

Topics: Amnion; Cyclooxygenase 2; Dinoprost; Dinoprostone; Extraembryonic Membranes; Female; Forkhead Box Protein M1; Forkhead Transcription Factors; Gene Expression; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; Matrix Metalloproteinase 9; Obstetric Labor, Premature; Pregnancy; Premature Birth; RNA, Messenger; RNA, Small Interfering

Infections with a strain of Escherichia coli producing Shiga toxins could be one of the causes of fetal morbidity and mortality in pregnant women. We have previously reported that Shiga toxin type 2 (Stx2) induces preterm delivery in pregnant rats. In this study, we evaluate the role of TNF-α, PGs and NO in the Stx2-induced preterm delivery.. Pregnant rats were treated with Stx2 (0.7 ng g(-1)) and killed at different times after treatment. Placenta and decidua were used to analyse NOS activity by the conversion of L-[(14)C]arginine into L-[(14)C]citrulline, levels of PGE(2) and PGF(2α) assessed by radioimmunoassay, and cyclooxygenase (COX) proteins by Western blot. TNF-α level was analysed in serum by ELISA and by cytotoxicity in L929 cells. The inhibitor of inducible NOS, aminoguanidine, the COX-2 inhibitor, meloxicam, and the competitive inhibitor of TNF-α, etanercept, were used alone or combined to inhibit NO, PGs and TNF-α production respectively, to prevent Stx2-induced preterm delivery.. Stx2 increased placental PGE(2) and decidual PGF(2α) levels as well as COX-2 expression in both tissues. Aminoguanidine and meloxicam delayed the preterm delivery time but did not prevent it. Etanercept blocked the TNF-α increase after Stx2 treatment and reduced the preterm delivery by approximately 30%. The combined action of aminoguanidine and etanercept prevented Stx2-induced preterm delivery by roughly 70%.. Our results demonstrate that the increased TNF-α and NO induced by Stx2 were the predominant factors responsible for preterm delivery in rats.

Topics: Animals; Cyclooxygenase 2; Decidua; Dinoprost; Dinoprostone; Drug Therapy, Combination; Etanercept; Female; Guanidines; Immunoglobulin G; Nitric Oxide; Placenta; Pregnancy; Premature Birth; Rats; Rats, Sprague-Dawley; Receptors, Tumor Necrosis Factor; Shiga Toxin 2; Tumor Necrosis Factor-alpha

A critical role of proinflammatory mediators including cytokines, prostaglandins, and extracellular matrix remodeling enzymes in the processes of human labor and delivery, at term and preterm, has been demonstrated. In nongestational tissues, apelin plays an important role in a number of physiologic processes, including the regulation of inflammation. However, the role and regulation of apelin and the apelin receptor (APJ) in human gestational tissues are not known. The aims of this study were to determine the effect of (i) preterm and term labor on apelin and APJ expression in human gestational tissues and (ii) apelin small interfering RNA (siRNA) knockdown in human primary amnion cells on prolabor mediators. Human placenta and fetal membranes were collected from term nonlaboring women and women after spontaneous labor and delivery. Preterm and term spontaneous labor were associated with significantly lower apelin expression in fetal membranes. On the other hand, there was no effect of labor on APJ expression and no effect of term labor on placental apelin or APJ expression. Transfection of primary amnion cells with apelin siRNA was associated with significantly increased interleukin (IL)-1β-induced IL-6 and IL-8 release and cyclooxygenase-2 messenger RNA (mRNA) expression and resultant prostaglandin E2 and prostaglandin F2α release. There was no effect of apelin siRNA on matrix metalloproteinase (MMP)-9 mRNA expression and pro MMP-9 release. In summary, human labor downregulates apelin expression in human fetal membranes. Furthermore, a role of apelin in the regulation of proinflammatory and prolabor mediators in human fetal membranes is supported by our studies.

Topics: Amnion; Apelin; Apelin Receptors; Cells, Cultured; Cyclooxygenase 2; Dinoprost; Dinoprostone; Down-Regulation; Female; Humans; Inflammation Mediators; Intercellular Signaling Peptides and Proteins; Interleukin-1beta; Interleukin-6; Interleukin-8; Matrix Metalloproteinase 9; Placenta; Pregnancy; Premature Birth; Receptors, G-Protein-Coupled; RNA Interference; RNA, Messenger; Signal Transduction; Term Birth; Transfection

To investigate the association between maternal oxidative stress at mid-gestation and subsequent development of pregnancy complications.. A total of 503 healthy pregnant women provided their blood and urine samples at 24 to 26 weeks of gestation and were prospectively followed through postpartum. These samples were used to assess a variety of oxidative stress markers, including plasma total antioxidant capacity, 8-isoprostane, erythrocyte glutathione peroxidase and superoxide dismutase activity, and urinary 8-hydroxydeoxyguanosine (8-OHdG).. Compared with women with uncomplicated pregnancies, significantly higher plasma 8-isoprostane levels were noted in women who developed preeclampsia (P = .008) and small-for-gestational age infants (P = .002), while higher urinary 8-OHdG concentrations were noted in women who subsequently had low-birth-weight neonates (<2500 g, P = .043).. Increased maternal oxidative stress at mid-gestation was associated with subsequent pregnancy complications.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Antioxidants; Biomarkers; Deoxyguanosine; Dinoprost; Erythrocytes; Female; Gestational Age; Glutathione Peroxidase; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Small for Gestational Age; Oxidative Stress; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Premature Birth; Prospective Studies; Superoxide Dismutase

Cord blood 8-isoprostane (8-IP) is a marker of lipid peroxidation in the peripartum period. The independent association with degree of prematurity is not well-described.. To identify patterns of lipid peroxidation among early, moderate and late preterm infants, and to understand how cord blood 8-IP varies with gestational age (GA) and related covariates.. Mother-infant pairs from 237 preterm births were studied as part of a longitudinal birth cohort study. GA subgroups were defined as extremely (≤28w), moderately (29-33w), and late (34-36w) preterm. Cord blood 8-IP was measured using EIA. Elevated 8-IP (4th quartile) was the primary outcome for multivariate logistic regression models, which were adjusted for maternal age/race, multiple gestation and infant gender, as well as other relevant covariates.. Elevated 8-IP was associated with extremely preterm birth (OR=4.31; 95% CI=1.90, 9.76), and was inversely associated with increasing GA (OR=0.88; 95% CI=0.80, 0.97). Elevated 8-IP was also associated with decreasing birth weight (BW), clinical chorioamnionitis, fetal inflammatory response of the placenta (FIR), and signs of perinatal depression. The GA on 8-IP association appeared to be modified by several maternal disease and fetal-infant factors. Lastly, the indirect associations between log-transformed 8-IP, GA and BW appeared to be most prominent for GA<30w and for BW<2000g.. Lipid peroxidation in preterm birth, and the relative influence of accompanying peripartum factors, varies according to degree of prematurity. These findings have important implications for the developmental regulation of antioxidant defense and its impact on neonatal outcomes.

Topics: Adult; Birth Weight; Dinoprost; Female; Fetal Blood; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Lipid Peroxidation; Male; Pregnancy; Premature Birth; Sex Factors

Increased oxygen tension at birth regulates physiologic events that are essential to postnatal survival, but the accompanying oxidative stress may also generate isoprostanes. We hypothesized that isoprostanes regulate ductus arteriosus (DA) function during postnatal vascular transition.. Isoprostanes were measured by gas chromatography-mass spectrometry. DA tone was assessed by pressure myography. Gene expression was measured by quantitative PCR.. Oxygen exposure was associated with increased 8-iso-prostaglandin (PG)F2α in newborn mouse lungs. Both 8-iso-PGE2 and 8-iso-PGF2α induced concentration-dependent constriction of the isolated term DA, which was reversed by the thromboxane A2 (TxA2) receptor antagonist SQ29548. SQ29548 pretreatment unmasked an isoprostane-induced DA dilation mediated by the EP4 PG receptor. Exposure of the preterm DA to 8-iso-PGE2 caused unexpected DA relaxation that was reversed by EP4 antagonism. In contrast, exposure to 8-iso-PGF2α caused preterm DA constriction via TxA2 receptor activation. Further investigation revealed the predominance of the TxA2 receptor at term, whereas the EP4 receptor was expressed and functionally active from mid-gestation onward.. This study identifies a novel physiological role for isoprostanes during postnatal vascular transition and provide evidence that oxidative stress may act on membrane lipids to produce vasoactive mediators that stimulate physiological DA closure at birth or induce pathological patency of the preterm DA.

Topics: Analysis of Variance; Animals; Animals, Newborn; Bridged Bicyclo Compounds, Heterocyclic; Dinoprost; Dinoprostone; Ductus Arteriosus; Ductus Arteriosus, Patent; Fatty Acids, Unsaturated; Female; Gas Chromatography-Mass Spectrometry; Gene Expression Profiling; Hydrazines; Isoprostanes; Mice; Myography; Oxidative Stress; Oxygen; Pregnancy; Premature Birth; Receptors, Prostaglandin E, EP4 Subtype; Receptors, Thromboxane A2, Prostaglandin H2; Vasodilation

Ascending placentitis results in premature birth and high foal mortality. By understanding how placentitis induces premature delivery, it may be possible to develop diagnostic markers and to delay premature delivery pharmacologically, thereby decreasing perinatal foal mortality.. To identify relationships between bacterial infection, inflammation and premature parturition in mares with experimentally induced placentitis.. Experiment 1: Concentrations of allantoic fluid prostaglandins (PGs) F2alpha and E2 were measured in 8 mares after intracervical inoculation with Streptococcus equi ssp. zooepidemicus (at Days 285-291 of gestation) until parturition and compared with controls (n = 4). Experiment 2: mRNA expression of interleukin (IL)-1beta, IL-6, tumour necrosis factor (TNF)-alpha and IL-8 in the chorioallantois from inoculated mares in Experiment 1 were compared with 7 mares that foaled normally.. Bacterial inoculation resulted in 7 aborted fetuses and birth of one premature, viable foal. Infection was associated with inflammation of the chorioallantois in the region of the cervical star, isolation of bacteria and high concentrations of PGE2 and PGF2alpha in allantoic fluid obtained within 48 h of delivery (P = 0.04). Chorioallantois from all mares expressed mRNA for IL-8, TNF-alpha, IL-6 and IL-1beta. Experimentally infected mares expressed more mRNA for IL-6 (P = 0.003) and IL-8 (P = 0.009) in the cervical star region and more mRNA for IL-6 (P = 0.004) in tissues from placental horns than control mares.. Bacterial placentitis may result in liberation of cytokines from the chorioallantois and prostaglandin formation leading to abortion or birth of a precociously mature foal.

Topics: Abortion, Veterinary; Animals; Bacterial Infections; Cytokines; Dinoprost; Dinoprostone; Female; Gene Expression Regulation; Horse Diseases; Horses; Inflammation; Placenta; Placenta Diseases; Pregnancy; Pregnancy Complications, Infectious; Premature Birth; RNA, Messenger

Organized uterine contractions, including those necessary for parturition, are dependent on calcium entry through voltage-gated calcium channels in myometrial smooth muscle cells. Recent evidence suggests that small-conductance Ca(2+)-activated potassium channels (K(Ca)2), specifically isoforms K(Ca)2.2 and 2.3, may control these contractions through negative feedback regulation of Ca(2+) entry. We tested whether selective pharmacologic activation of K(Ca)2.2/2.3 channels might depress uterine contractions, providing a new strategy for preterm labor intervention. Western blot analysis and immunofluorescence microscopy revealed expression of both K(Ca)2.2 and K(Ca)2.3 in the myometrium of nonpregnant (NP) and pregnant (gestation day 10 and 16; D10 and D16, respectively) mice. Spontaneous phasic contractions of isolated NP, D10, and D16 uterine strips were all suppressed by the K(Ca)2.2/2.3-selective activator CyPPA in a concentration-dependent manner. This effect was antagonized by the selective K(Ca)2 inhibitor apamin. Whereas CyPPA sensitivity was reduced in D10 and D16 versus NP strips (pIC(50) 5.33 ± 0.09, 4.64 ± 0.03, 4.72 ± 0.10, respectively), all contractions were abolished between 30 and 60 μM. Blunted contractions were associated with CyPPA depression of spontaneous Ca(2+) events in myometrial smooth muscle bundles. Augmentation of uterine contractions with oxytocin or prostaglandin F(2α) did not reduce CyPPA sensitivity or efficacy. Finally, in an RU486-induced preterm labor model, CyPPA significantly delayed time to delivery by 3.4 h and caused a 2.5-fold increase in pup retention. These data indicate that pharmacologic stimulation of myometrial K(Ca)2.2/2.3 channels effectively suppresses Ca(2+)-mediated uterine contractions and delays preterm birth in mice, supporting the potential utility of this approach in tocolytic therapies.

Topics: Abortifacient Agents; Animals; Apamin; Calcium; Dinoprost; Female; Mice; Mice, Inbred C57BL; Mifepristone; Myometrium; Obstetric Labor, Premature; Oxytocin; Potassium Channels, Calcium-Activated; Pregnancy; Premature Birth; Pyrazoles; Pyrimidines; Uterine Contraction

Many signaling pathways that contribute to tumorigenesis are also functional in pregnancy, although they are dysregulated in the former and tightly regulated in the latter. Transformation-related protein 53 (Trp53), which encodes p53, is a tumor suppressor gene whose mutation is strongly associated with cancer. However, its role in normal physiological processes, including female reproduction, is poorly understood. Mice that have a constitutive deletion of Trp53 exhibit widespread development of carcinogenesis at early reproductive ages, compromised spermatogenesis, and fetal exencephaly, rendering them less amenable to studying the role of p53 in reproduction. To overcome this obstacle, we generated mice that harbor a conditional deletion of uterine Trp53 and examined pregnancy outcome in females with this genotype. These mice had normal ovulation, fertilization, and implantation; however, postimplantation uterine decidual cells showed terminal differentiation and senescence-associated growth restriction with increased levels of phosphorylated Akt and p21, factors that are both known to participate in these processes in other systems. Strikingly, uterine deletion of Trp53 increased the incidence of preterm birth, a condition that was corrected by oral administration of the selective COX2 inhibitor celecoxib. We further generated evidence to suggest that deletion of uterine Trp53 induces preterm birth through a COX2/PGF synthase/PGF(2alpha) pathway. Taken together, our observations underscore what we believe to be a new critical role of uterine p53 in parturition.

Topics: Animals; Celecoxib; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Decidua; Dinoprost; Embryo Implantation; Female; Fertilization; Hydroxyprostaglandin Dehydrogenases; Mice; Mice, Transgenic; Ovulation; Pregnancy; Premature Birth; Proto-Oncogene Proteins c-akt; Pyrazoles; Sulfonamides; Tumor Suppressor Protein p53

Lipopolysaccharide (LPS)-stimulated TNFalpha production is reported to be greater for whole blood (WB) cultures prepared from patients with a history of preterm birth than cultures obtained from women with a history of term birth. The objectives of this study were (1) to determine if there is a similar differential responsiveness for peripheral blood mononuclear leukocytes (PBML) and (2) to determine if treatment with aspirin influences LPS-stimulated TNFalpha production in these patients. WB and PBML were obtained from women with a history of preterm delivery before 32 weeks (cases; n=5) and age- and race-matched controls (n=5) with a history of uncomplicated term delivery. WB and PBML were cultured and stimulated with LPS. All participants then took aspirin daily for 1 week and responsiveness of PBML and WB cultures to LPS was retested. The history of preterm labor was found to have no effect on LPS-stimulated TNFalpha production in cultures of WB or PBML. Aspirin treatment enhanced LPS-stimulated TNFalpha production by PBML from controls but not cases. We conclude that endotoxin responsiveness of women with a history of preterm birth is similar to that of women with a history of term birth in terms of in vitro TNFalpha production. Aspirin increases TNFalpha production by PBML in control women but not in women with a history of preterm birth. The divergent responses to aspirin treatment in patients with and without prior preterm labor may reflect differential regulation of cytokine production by prostaglandins in women with preterm labor associated with infection or inflammation.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Blood Cells; Case-Control Studies; Cells, Cultured; Dinoprost; Female; Humans; Leukocytes, Mononuclear; Lipopolysaccharides; Lymphocyte Activation; Pregnancy; Premature Birth; Tumor Necrosis Factor-alpha

The blackbuck (Antilope cervicapra) is a small (20-30 kg) Indian antelope that is listed on Schedule I of the Indian Wildlife Protection Act, 1972. Studies were undertaken to develop assisted reproductive technologies, such as synchronisation of oestrus and non-surgical AI, to support the conservation and genetic management of this Indian antelope. Semen characteristics, testosterone levels and the feasibility of short-term cold storage of semen were investigated. Furthermore, different oestrous synchronisation protocols (norgestomet implants and prostaglandin injections) were evaluated for successful AI, defined as the birth of live young. Norgestomet ear implants and i.m. administration of pregnant mare's serum gonadotropin (PMSG) resulted in successful pregnancies in two of five inseminated females, but both had twin pregnancies that were delivered prematurely. In contrast, two injections of prostaglandin 11 days apart were effective in synchronising oestrus in the blackbuck. Transcervical AI in oestrous-synchronised animals 72 and 96 h after the second prostaglandin injection resulted in successful pregnancies in four of six inseminated females (67%) and resulted in the delivery of three live fawns. These studies demonstrate the potential application of AI technology for the conservation of endangered ungulates. To our knowledge, this is the first report regarding the synchronisation of oestrus and successful non-surgical AI in blackbuck.

Topics: Animals; Antelopes; Cold Temperature; Conservation of Natural Resources; Dinoprost; Drug Implants; Estrus Synchronization; Feasibility Studies; Female; Fertility Agents, Female; Gonadotropins, Equine; Injections, Intramuscular; Insemination, Artificial; Live Birth; Male; Pregnancy; Pregnenediones; Premature Birth; Semen; Semen Analysis; Semen Preservation; Sperm Count; Sperm Motility; Spermatozoa; Testosterone; Time Factors; Twins

The objectives of this study were to determine whether oxidative stress early in pregnancy influenced pregnancy outcome. A combination of assays were used for exogenous and endogenous anti-oxidants together with two well accepted biomarkers for oxidative stress, the urinary excretion of 8-iso-PGF(2alpha) (a biomarker marker for lipid oxidation, n=508) and 8-oxo-7,8 dihydro-2 deoxyguanosine (8-OHdG, a biomarker for DNA oxidation, n=487). The two biomarkers tracked different pregnancy outcomes. Isoprostanes were associated with an increased risk of pre-eclampsia and a decreased proportion of female births. In contrast, 8-OHdG tracked lower infant birthweight and shortened gestation duration. Birth defects were associated with low levels of 8-OHdG.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Antioxidants; Biomarkers; Birth Weight; Congenital Abnormalities; Deoxyguanosine; Dinoprost; DNA Damage; Female; Gestational Age; Humans; Infant, Newborn; Lipid Peroxidation; Male; Middle Aged; Oxidants; Oxidative Stress; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Prospective Studies; Young Adult

Management of preterm labor by tocolysis remains an unmet medical need. Prostaglandins play a major role in regulation of uterine activity and in molecular mechanisms of human labor and parturition. There is some circumstantial evidence that prostaglandin F2alpha by action through the prostaglandin receptor subtype FP is effective in key events during labor uterine contraction, rupture of membranes and cervical dilation. This role of FP is briefly reviewed. In this study, we tested the hypothesis that an orally active and selective FP antagonist may arrest labor and delay parturition in animal models.. We examined the effects of a small molecule selective antagonist of the FP receptor (AS604872) in inhibition of spontaneous uterine contraction in pregnant rat near term. We tested AS604872 for its ability to delay preterm birth in a mouse model in which the anti-progestin agent RU486 triggered parturition.. By oral or intravenous dosing AS604872 reduced markedly and dose-dependently the spontaneous uterine contractions in late-term pregnant rats at gestational days 19-21. In pregnant mice, AS604872 delayed the preterm birth caused by RU486 administration. The effect was dose-dependent with a significant increase in the mean delivery time of 16 and 33 hours at oral doses of 30 mg/kg and 100 mg/kg, respectively, in the case of labor triggered at gestational day 14. In both models AS604872 appeared more effective than the beta-agonist ritodrine.. The tocolytic activity displayed by a selective FP receptor antagonist supports a key role for the FP receptor in the pathophysiology of premature birth and demonstrates the therapeutic potential of an FP antagonist for the treatment of preterm labor cases in which uterine hyperactivity plays a dominant role.

Topics: Administration, Oral; Animals; Biphenyl Compounds; Delayed-Action Preparations; Dinoprost; Dose-Response Relationship, Drug; Female; Injections, Intravenous; Pregnancy; Pregnancy, Animal; Premature Birth; Rats; Rats, Sprague-Dawley; Sulfonamides; Tocolytic Agents; Treatment Outcome; Uterine Contraction

This study examined the reliability of assessing clinical periodontal measures on third molars, and the association between oral inflammation with periodontal pathology including third molars, and systemic inflammation including negative obstetric outcomes.. Reliability of third molar probing depth (PD) was assessed for 41 patients by trained examiners. The data for the association between oral inflammation with periodontal pathology and systemic outcomes were derived from an IRB-approved study, "Oral Conditions and Pregnancy." Full mouth periodontal exams including third molars were conducted at less than 24 weeks of pregnancy. Periodontal status, moderate/severe periodontal disease (15 or more sites PD > or =4 mm) was considered as a possible predictor of systemic inflammation and pre-term birth. The upper quartile of the extent of PD for third molars alone (PD > or =4 mm) also was considered as a possible exposure variable for the same outcomes. Chi-square and t tests were used to determine statistical significance (0.05). Significant predictor variables were included in multivariate models. Unconditional logistic multivariate models were used to derive odds ratios (OR) and 95% confidence intervals (CI).. Reliability of PD within 1 mm was excellent, and similar for third molars and non-third molars. Data from 1,020 obstetric patients were available for analysis. Eighteen percent of the patients delivered preterm, at less than 37 weeks. Having moderate/severe periodontal disease excluding third molars, was significantly associated with preterm birth (P = .008). Results were more significant if third molars were included (P = .0005). With multivariate models moderate/severe periodontal disease at enrollment including third molar PD, was associated with preterm birth (OR, 1.7; 95% CI, 1.1, 2.6). If only the extent of third molar PD was considered, odds also were increased for preterm birth (OR, 2.4; 95% CI, 1.1, 5.2). If only the extent of third molar PD was considered at enrollment, odds were increased for serum markers of systemic inflammation, elevated serum CRP, and oxidative stress, 8-isoPGF(2alpha).. Dental examiners could reliably assess clinical periodontal measures on third molars. Third molars should be included in studies of systemic outcomes associated with oral inflammation. Women of child-bearing age should be made aware of the systemic risks of oral inflammation with third molar periodontal pathology.

Topics: Adult; C-Reactive Protein; Dinoprost; Female; Humans; Logistic Models; Molar, Third; Odds Ratio; Periodontitis; Pregnancy; Premature Birth; Reproducibility of Results

In sheep, parturition is initiated by increased fetal hypothalamic-pituitary-adrenal axis (HPAA) activity leading to PGE(2) and PGF(2alpha) production and a rise in the 17beta-estradiol-progesterone (E(2)/P(4)) ratio. Uteroplacental PG production can also increase fetal HPAA activity. Periconceptional maternal undernutrition accelerates fetal HPAA maturation resulting in preterm labor. We determined whether preterm labor was preceded by an increase in PG concentrations and E(2)/P(4) ratio and whether these increases preceded or followed the corresponding rise in cortisol concentrations. Singleton-bearing ewes were nourished ad libitum (N, n = 9) or undernourished (UN, n = 10) to reduce maternal weight by 15% from -61 days (d) to +30 d after mating with ad libitum intake thereafter. Paired maternal and fetal blood samples were collected from 126 d until delivery. Half the UN group delivered prematurely (>2 SD below mean gestation for the flock). PG and cortisol concentrations and E(2)/P(4) ratio increased before delivery in the same way in both groups. However, the increases occurred 7-10 d earlier in UN than in N animals. In both UN and N fetuses cortisol concentrations rose before fetal and maternal PG concentrations and maternal E(2)/P(4) ratio. Periconceptional maternal undernutrition induces preterm delivery in sheep by advancing the expected prepartum rise in cortisol and PG concentrations and E(2)/P(4) ratio. The rise in fetal cortisol concentration precedes the rise in fetal and maternal PG concentrations and maternal E(2)/P(4) ratio, suggesting that the underlying mechanism is likely to be acceleration of fetal HPAA maturation, resulting in initiation of the normal process of parturition.

Topics: Animals; Animals, Newborn; Dinoprost; Dinoprostone; Estradiol; Female; Fetal Blood; Food Deprivation; Gestational Age; Parturition; Pregnancy; Premature Birth; Prenatal Nutritional Physiological Phenomena; Progesterone; Sheep

A novel prostaglandin F2alpha receptor antagonist, THG113.31, was tested for the suppression of uterine contractility and delay of preterm labor in sheep.. We determined the tocolytic effectiveness of THG113.31 on contractions that were stimulated in vitro by prostaglandin F2alpha and E2 in longitudinal and circular myometrial strips. We also tested the ability of THG113.31 in vivo to lower uterine electromyographic activity that was induced by the progesterone receptor blocker, RU486, and to delay preterm birth.. THG113.31 suppressed the amplitude of prostaglandin F2alpha, but not prostaglandin E2-induced contractions of both circular and longitudinal myometrium (P<.01). The times to delivery after RU486 were 34.8+/-1.1 hours (saline solution) and 41.9+/-0.5 hours (THG113.31; P<.001) or an average delay of 7.1 hours. There were no changes in fetal blood gases (PaO2 , PaCO2 , pH, or SaO2) because of THG113.31. Fetal cortisol levels rose in each group, and fetal and maternal prostaglandin E2 and F2alpha metabolite concentrations rose similarly in both groups.. THG113.31 specifically suppresses prostaglandin F2alpha-induced myometrial contractility and delays delivery.

Topics: Animals; Delivery, Obstetric; Dinoprost; Dinoprostone; Electromyography; Female; Fetal Blood; Hydrocortisone; In Vitro Techniques; Mifepristone; Myometrium; Peptides; Pregnancy; Pregnancy, Animal; Premature Birth; Receptors, Progesterone; Receptors, Prostaglandin; Sheep; Time Factors; Tocolytic Agents; Uterine Contraction; Uterus