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Background: During pregnancy and parturition a remodeling within the extracellular matrix of the cervix and the corpus uteri occurs, which is of fundamental importance to a normal labor. The aim of this study is to identify the major proteoglycans in corpus uteri of non-pregnant subjects.Methods: From human uterine tissue proteoglycans were extracted and purified using CsCl-density gradient centrifugation, gel and ion-exchange chromatography. The proteoglycans were quantified and identified by Alcian Blue before and after ABC-digestion and by Western blotting.Results: The results showed that the corpus uteri contains a substantial amount of proteoglycans, 1.825 microg/mg wet weight. Decorin is dominating, constituting 63% of the total amount of proteoglycans. Heparan sulphate proteoglycans accounted for 20% and biglycan for 16%. Less than 1% consisted of the large proteoglycan versican.Conclusions: Further investigations must be performed to provide more information of the biological role of the proteoglycans in the uterus, especially during labor, by the presence of heparan sulphate proteoglycans and the minute presence of versican which indicate that the proteoglycan composition and organization is different to that of the cervix. [ABSTRACT FROM AUTHOR]

Introduction: Anti-secretory factor is a protein that regulates secretory and inflammatory processes and preterm birth is associated with inflammation. Therefore, our hypothesis was that anti-secretory factor might play a role in immune reactivity and homeostasis during pregnancy., Material and Methods: Following spontaneous onset of labor and preterm or term delivery, placenta biopsies were collected. The levels of anti-secretory factor and markers of inflammation (CD68, CD163) and vascularization (CD34, smooth muscle actin) were analyzed by immunohistochemistry., Results: The 61 placental biopsies included 31 preterm (<37 weeks of gestation) and 30 term (37-41 weeks) samples. The preterm placentas exhibited lower levels of anti-secretory factor (p = 0.008) and larger numbers of CD68-positive cells (p < 0.001) compared to term. Preterm placentas had blood vessel of smaller diameter (p = 0.036) indicative of immaturity. The level of interleukin-6 in cord blood was higher after very preterm than term birth, suggesting a fetal inflammatory response. The placenta level of anti-secretory factor was positively correlated to the length of gestation (p = 0.025) and negatively correlated to the levels of the inflammatory markers CD68 (p = 0.015) and CD163 (p = 0.028)., Conclusions: Preterm delivery is associated with low levels of anti-secretory factor in placenta. Inflammation, a potential trigger of preterm birth, is more pronounced in the preterm placenta and inversely related to the placental level of anti-secretory factor, suggesting both a link and a potential target for intervention., (© 2017 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: To investigate expression and localization of prostaglandin receptors EP1-4 and FP and localization of stromal factors CTGF (connective tissue growth factor), furin, calgranulin B and ALOX15 (arachidonate 15-lipooxygenase) in human cervical tissue from post-term women with failed or successful labor induction after prostaglandin priming., Design: Experimental prospective clinical study., Setting: Tertiary obstetric care center., Population: Twenty-six women giving birth post-term, with failed or successful labor induction, and a control group consisting of 19 women with spontaneous onset of labor and delivery at term., Methods: Biopsies were obtained from post-term women with successful (responders; R) and failed (non-responders; NR) labor induction. Women with spontaneous delivery at term were included as controls (C). mRNA expression was determined with real time PCR, protein expression and localization with immunohistochemistry., Main Outcome Measures: Comparisons of mRNA and protein expressions between post-term pregnancies with failed and successful labor induction as well as term controls., Results: EP4 mRNA expression was down-regulated concomitant with an up-regulation of EP3 mRNA expression in cervix from the NR group as compared with the R group. In stroma, immunoreactivity of the EP4 protein was increased in the NR group as compared with R and C groups., Conclusions: Failure of cervical ripening, after local application of prostaglandins for labor induction, may be caused by the increased expression of EP3 and concomitant decrease in EP4 expression., (© 2013 Nordic Federation of Societies of Obstetrics and Gynecology.)

Background: Computerized ST analysis of fetal electrocardiography (ECG) combined with cardiotochography (CTG) has been introduced for intrapartum monitoring and is the prevailing method when ST analysis (STAN®) is used., Objective: To assess the evidence that computerized ST analysis during labor reduces the incidence of fetal metabolic acidosis, hypoxic ischemic encephalopathy, cesarean section, instrumental vaginal delivery or the number of instances where fetal scalp blood sampling is used as compared with CTG only., Methods: Search of PubMed, Cochrane Library, EMBASE, Web of Science, CINAHL and CRD databases., Selection Criteria: CTG only compared with CTG + computerized ST analysis., Data Collection and Analysis: Studies were assessed using pre-designed templates. Meta-analyses of included randomized controlled trials were performed using a random effects model., Results: Risk ratio for cord metabolic acidosis with STAN® was 0.96 [95% confidence interval (CI) 0.49-1.88]. Risk ratio for cesarean sections or instrumental vaginal deliveries for fetal distress was 0.93 (95%CI 0.80-1.08) and for fetal scalp blood sampling 0.55 (95%CI 0.40-0.76). Encephalopathy cases were not assessed due to their low incidence., Conclusions: There is not enough scientific evidence to conclude that computerized ST analysis reduces the incidence of metabolic acidosis. Cesarean sections and instrumental vaginal deliveries due to fetal distress or other indications are the same, regardless of method, but STAN® reduces the number of instances which require scalp blood sampling., (© 2012 The Authors © 2012 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: To investigate risk factors associated with postterm pregnancy and cesarean delivery following labor induction., Design: Population-based cohort study., Setting: Sweden., Population: From the Swedish Medical Birth Register, a total of 1,176,131 singletons births from gestational week 37 and onwards, between 1992 and 2006., Methods: Unconditional logistic regression analysis., Main Outcome Measures: Risk of postterm pregnancy (delivery at >or=42 weeks) and cesarean delivery following labor induction., Results: Among 1,176,131 births, 8.94% were delivered postterm. Compared to normal weight women, the risk of postterm pregnancy in obese women was almost doubled (adjusted OR: 1.63, 95% CI 1.59-1.67). The risk of postterm pregnancy increased with increasing maternal age and was higher among primiparous women. The risk of cesarean section (CS) following labor induction postterm, increased with maternal age and BMI, and was more than doubled among women 35 years and older (adjusted OR 2.28, 95% CI 2.04-2.56). A fivefold risk of CS was seen among nulliparous women (adjusted OR 5.05, 95% CI 4.71-5.42). Parous women with a previous CS undergoing labor induction had a sevenfold increased risk of CS postterm (adjusted OR 7.19, 95% CI 5.93-8.71)., Conclusions: Nulliparity, advanced maternal age and obesity were the strongest risk factors for postterm pregnancy and CS following labor induction in postterm pregnancy. Including maternal risk factors to the cervical assessment may improve prediction of vaginal delivery following labor induction in postterm pregnancy.

Dalteparin, a low molecular weight heparin (LMWH), is given to pregnant women with thrombotic disorders. Clinical observations together with the documented changes of heparan sulfate proteoglycans in normal and protracted labor fostered the idea that LMWH shortens delivery time. Labor time was retrospectively determined among nulliparous pregnant women treated with dalteparin because of previous venous thromboembolism (VTE), thrombophilia or acute VTE during current pregnancy. Their labor time was compared to matched untreated controls. The proportion of instrumental deliveries and neonatal outcome was also compared. The dalteparin-treated group showed a significantly (30%) shorter labor time compared to matched controls. Total instrumental deliveries were the same in the two groups but operative intervention due to protracted labor was significantly less common in dalteparin-treated women. There was no difference in neonatal outcome. Dalteparin most likely shortens parturition time and may decrease the number of operative interventions due to protracted labor.

Objectives: The low molecular weight heparin, Dalteparin, shortens human labor time. The aim of this study was to investigate if the mechanism behind this effect involves myometrial contractility and cervical ripening and if the anticoagulative activity is necessary for its effect., Design: Experimental in vitro study., Setting: Lund University and Karolinska Institute, Sweden., Methods: The effect of low molecular weight heparins with or without anticoagulative properties on myometrial contractility was measured in vitro on smooth muscle strips from biopsies obtained at elective cesarean sections. The effects on cervical ripening were assessed in cervical fibroblasts cultured from explants of cervical biopsies obtained at delivery., Main Outcome Measures: Mean force and number of contractions in uterine smooth muscle strips and interleukin-8 (IL-8) secretion in cervical fibroblasts., Results: Myometrial smooth muscle strips pretreated with low molecular weight heparins showed increased contractile activity compared to untreated smooth muscle strips. Secretion of IL-8 from cultured cervical fibroblasts was significantly increased after treatment with low molecular weight heparin. Both these effects were independent of anticoagulative activity of the low molecular weight heparin., Conclusions: A possible underlying mechanism for the shortened labor time after low molecular weight heparin treatment is enhanced myometrial contractility and an increased IL-8 secretion in cervical fibroblast, mimicking the final cervical ripening in vivo. Our data support the notion that anticoagulant activity is not required to promote labor.

Objective: An extensive remodeling of the human cervical connective tissue occurs throughout pregnancy, with a decrease in the total concentration of collagen and proteoglycans. We hypothesized that the profound changes in proteoglycan production in the cervix would be seen in corresponding cervical fibroblasts as well., Methods: Cervical biopsies were obtained from five non-pregnant women, five women undergoing elective Cesarean section, six women directly after spontaneous term parturition and four directly after spontaneous preterm parturition. By explant technique, fibroblasts were cultured from the biopsies. Subcultures of the primary fibroblasts were treated with antibodies to heparan sulfate proteoglycans and labeled with radioactive sulfate. The labeled proteoglycans were purified by ion-exchange chromatography and separated by gel electrophoresis., Results: Proteoglycan production was reduced by 50% in fibroblasts obtained from term and preterm women. In comparison to equivalent control cultures from non-pregnant women, this decline was significant. Production of the proteoglycans biglycan and perlecan was similar in term partal and preterm partal cell cultures. Biglycan production was significantly reduced (by 40%) and perlecan production was significantly induced (by 60%) compared to control cultures. Fibroblast cultures established from women with preterm delivery had significantly higher production of heparan sulfate proteoglycans than those obtained from non-pregnant donors. Heparan sulfate proteoglycans were localized to cell membranes and intracellular compartments., Conclusions: The changes in proteoglycan production in the human pregnant cervix can also be seen in corresponding cervical fibroblasts. Term partal and preterm partal cells differed from their non-pregnant counterpart, which suggests a role for proteoglycans in cervical ripening.

Hypothesis: Proteoglycans are well-known modulators of intercellular communication and signaling. Remodeling of the proteoglycans in the human uterus occurs throughout pregnancy, and during labor. We therefore hypothesize that heparan sulfate proteoglycans (HSPGs) play an important role in establishing normal labor. In this study HSPGs were characterized and localized in human uterine tissue., Methods: Uterine biopsies were obtained from four nonpregnant women, four women during elective cesarean section and four during emergency cesarean section. The biopsies were extracted using 4 m guanidinium hydrochloride (GuHCL). HSPGs were then purified by repeated ion-exchange chromatography on dehydroepiandrosterone (DEAE)-cellulose after digestion with chondroitinase ABC and finally precipitated with Alcian blue. HSPGs were identified by agarose gel electrophoresis and Western blotting. Controlled degradation of the heparan sulfate (HS) side-chains was performed using heparitinase or deglycosylation with trifluoromethanesulfonic acid (TFMS). The resulting core proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and visualized by Coomassie staining. HSPGs were localized in uterine tissue by immunohistochemistry., Results: SDS-PAGE after deglycosylation indicated the presence of multiple distinct core proteins tentatively identified as syndecans 1-4 and glypican 1. Western blots confirmed the presence of these proteoglycans and also perlecan. Immunohistochemistry revealed that the HSPGs were localized mainly in the smooth muscle with few in the extracellular matrix (ECM). Syndecan 3, the dominant proteoglycan, showed the most pronounced changes during pregnancy and labor., Conclusion: For the first time several heparan sulfate proteoglycans have been identified and localized in the human uterus and shown to vary in expression during pregnancy and labor. Syndecan 3 had the most outstanding features in this respect.

Background: The aim of this study was to investigate the occurrence and appearance of the anastomosis between the two umbilical arteries in placentas from infants small for gestational age (SGA)., Methods: The arterial systems of 64 placentas from singleton pregnancies resulting in SGA infants were visualized by angiography. The method allowed study of the anastomosis between the umbilical arteries and calculation of the relative placental area supplied by each artery. The results were compared with findings in a previous study of appropriate for gestational age (AGA) infants. One-way analysis of variance (ANOVA) and chi2-analyses were used for statistics., Results: In 56 placentas the anastomosis was represented by a true vessel, in two by a fenestration, and in another two cases by fusion of the umbilical arteries. The anastomosis was absent in one case and another three cases had a single umbilical artery (SUA). When the diameter of the anastomosis was thinner than that of the umbilical arteries, their supply areas were significantly (p < or = 0.001) more symmetrical than in cases with a wider anastomosis. The anatomy of the anastomosis and the relationship between its width and the symmetry between the supply areas of each umbilical artery did not differ in placentas from SGA and AGA infants, despite various types of cord insertion and placentation., Conclusion: Static measurements of Hyrtl's anastomosis do not indicate a contributing part for intrauterine growth retardation.

Objective: To study whether stress urinary incontinence after menopause is correlated to changes in the paraurethral connective tissue ultrastructure and metabolism., Methods: Transvaginal biopsies were obtained from the paraurethral connective tissue in stress urinary incontinent women after menopause with and without estrogen replacement therapy, and from comparable controls. All the stress-incontinent women underwent urodynamic investigation. In the specimens, collagen concentration, measured as hydroxyproline, and the degree of extractability by pepsin digestion, were quantified. Proteoglycan composition and concentration were analyzed using Alcian Blue precipitation, followed by electro-phoretic separation and quantification. Using Northern blots, mRNA levels for the collagens I and III, the small proteoglycans decorin and biglycan, and the large proteoglycan versican, were quantified. Collagen structure was examined with transmission electron microscopy, and the diameters of collagen fibrils were analyzed with an interactive image analysis system (IBAS, Zeiss/Kontron)., Results: No significant difference in paraurethral connective tissue biochemistry or ultrastructure was registered between women with stress incontinence and controls. Estrogen replacement therapy resulted in a lower collagen concentration both between the controls (p = 0.02) and between the incontinent women (0.02). In the women with stress incontinence also the extractability by pepsin digestion was higher in the group with estrogen treatment (p = 0.004), indicating a decrease in cross-linking. The proteoglycan/collagen ratio was higher in the control group with estrogen treatment compared to untreated (p = 0.02), but no difference was found between estrogen treated and untreated incontinent women. The median collagen fibril diameter was 15% larger in the incontinent group of women without estrogen therapy compared to the control group and 5% larger when comparing the incontinent group on estrogen replacement therapy to the corresponding control group., Conclusion: The extracellular matrix of paraurethral connective tissue in stress urinary incontinent women after menopause reacted differently to estrogen replacement therapy compared to continent controls. In contrast to incontinent women of fertile age no major changes in collagen metabolism were found in stress urinary incontinent women after menopause.

In this prospective study, 56 women (2.3%) of 2,358 (47% nulliparous and 53% multiparous) delivered during a 12-month period at the Department of Obstetrics and Gynecology, Malmö General Hospital, had symptoms of carpal tunnel syndrome during pregnancy. All (33 nulliparous and 23 multiparous women) were examined, at the outpatient's maternity care unit and within 4-5 weeks from the time of debut of symptoms, by a specialist in hand surgery. At that time the most common symptoms were paresthesia and nocturnal pain. Twenty-nine had signs of reduced sensibility and 14 of them had a positive two-point discrimination test. All had generalized edema. Conservative treatment with splinting of the wrist at night made 46 out of 56 symptom-free. Of the remaining 10 women, 3 had to be operated on, whereas 7 received only conservative treatment, as the expected time for parturition was very close. One of them had to be operated on after delivery. In conclusion, carpal tunnel syndrome during pregnancy is most common in primiparas with generalized edema. Conservative treatment is sufficient for symptom relief in most women (80%) but a few cases need operative intervention to abolish the severe pain and to avoid disturbances of hand function.