Nitric oxide synthase activity in human trophoblast, term placenta and pregnant myometrium

To investigate the possible role of nitric oxide (NO) produced locally or intramurally in the quiescence of the pregnant myometrium, nitric oxide synthase (NOS) activity was measured in samples from first trimester (villous, and non villous-trophoblast), term placenta and pregnant myometrium. Trophoblast tissue was obtained from psychosocial termination of pregnancy (9 – 12 weeks' gestation) whereas placenta and myometrium, from the same patient, at deliveries by Caesarean section. NOS activity was measured in both cytosolic and particulate fractions by the formation of (14)C-citrulline from (14)C-arginine. Western immunoblotting was used to identify the endothelial NOS (eNOS) and neuronal (nNOS) isoforms. The activity of NOS in particulate fractions from all preparations was considerably higher than the cytosolic fractions. Activity in all fractions except the myometrium was highly Ca-dependent. More than 50% of particulate NOS from the myometrium was Ca-independent. NOS activity was highest in the villous trophoblast and there was a significant difference between the villous and non-villous trophoblast. In placenta and myometrium, NOS was 2–4 fold and 20–28-fold lower than the villous trophoblast, respectively. Western blot analysis showed clearly eNOS in the particulate fraction and a weak eNOS band in the cytosolic fractions, whereas nNOS was not detectable in any of the fractions. In view of the marginal activity of NOS in the myometrium, NO produced by the trophoblast and placenta could play a significant role in maintaining uterine quiescence by paracrine effect

Allergen-specific IgE over time in women before, during and after pregnancy

The trajectory of IgE levels before, during and after pregnancy in sensitized individuals is characterized by significant increase in specific IgE to birch allergens but not to other allergens after multiple testing. This increase may warrant some surveillance in the antenatal care for those with clinical symptoms.The Swedish Research CouncilThe Swedish initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) framework grant no 340-2013-5867Stockholm County Council (ALF-projects)The Strategic Research Program in Epidemiology at Karolinska InstitutetDepartment of Clinical Sciences at Danderyd HospitalSwedish Medical Research CouncilSwedish Heart-Lung FoundationSwedish Asthma and Allergy Association’s Research FoundationAccepte

Limited association between markers of stress during pregnancy and fetal growth in “Born into Life”, a new prospective birth cohort

AIMS: We aimed to investigate the associations between perceived maternal stress or salivary cortisol levels during pregnancy and birth weight. METHODS: In 2010-2012 we recruited 92 women living in Stockholm, Sweden, and followed them from before conception and through pregnancy and childbirth. Their Perceived Stress Scale (PSS) scores and salivary cortisol levels were collected at 26-28 gestational weeks. Birth weight was collected from medical records. Linear regression analyses and Pearson correlations were performed between the PSS scores or cortisol levels and birth weight respectively, adjusted for gestational age. RESULTS: No significant associations were found between PSS scores or cortisol levels and birth weight. There was a trend towards higher salivary cortisol levels among infants with lower birth weights and this effect was attenuated after adjusting for gestational age. Morning cortisol levels (r=-0.31, p=0.01), the decline in cortisol levels (r=-0.26, p=0.03) and evening cortisol levels (r=-0.21, p=0.09) were negatively correlated with PSS scores. CONCLUSION: Maternal stress during pregnancy was not associated to birth weight. The inverse correlation between PSS scores and cortisol levels may indicate other mechanisms for maternal stress on child outcomes than the previous explanation of hypothalamic-pituitary-adrenal axis activity.Swedish Initiative for Research on Microdata in the Social and Medical Sciences (SIMSAM) framework grant no 340-2013-5867, as well as the Swedish Heart Lung Foundation, the Swedish Asthma and Allergy Association’s Research Foundation, grants provided by the Stockholm County Council (ALF project), FORTE, and the Strategic Research Program in Epidemiology at Karolinska Institutet.Accepte

Limited association between markers of stress during pregnancy and fetal growth in 'Born into Life' : a new prospective birth cohort

Aims: We aimed to investigate the associations between perceived maternal stress or salivary cortisol levels during pregnancy and birthweight. Methods: In 2010-2012, we recruited 92 women living in Stockholm, Sweden, and followed them from before conception and through pregnancy and childbirth. Their Perceived Stress Scale (PSS) scores and salivary cortisol levels were collected at 26-28 gestational weeks. Birthweight was collected from medical records. Linear regression analyses and Pearson correlations were performed between the PSS scores or cortisol levels and birthweight, respectively, adjusted for gestational age. Results: No significant associations were found between PSS scores or cortisol levels and birthweight. There was a trend towards higher salivary cortisol levels among infants with lower birthweights, and this effect was attenuated after adjusting for gestational age. Morning cortisol levels (r = -0.31, p = 0.01), the decline in cortisol levels (r = -0.26, p = 0.03) and evening cortisol levels (r = -0.21, p = 0.09) were negatively correlated with PSS scores. Conclusion: Maternal stress during pregnancy was not associated with birthweight. The inverse correlation between PSS scores and cortisol levels may indicate other mechanisms for maternal stress on child outcomes than the previous explanation of hypothalamic-pituitary-adrenal axis activity.Swedish Research CouncilSwedish Initiative for Research on Microdata in the Social and Medical Sciences framework (grant no 340-2013-5867)Swedish Heart Lung FoundationSwedish Asthma and Allergy Association's Research FoundationStockholm County Council ALF-projectsFORTEFORMASStrategic Research Program in Epidemiology at Karolinska InstitutetAccepte

Normal values for calprotectin in stool samples of infants from the population-based longitudinal born into life study

Faecal calprotectin is a protein used as a diagnostic marker for inflammatory bowel diseases. We determined upper limits for normal calprotectin values for neonatal, 6, 12 and 24 months old children using a turbidimetric immunoassay in a cohort of Swedish children. The advantage of the method is that opposite to previously used enzyme-linked immunosorbent assay (ELISA) method, it enables measuring single samples, and thus, shortens the analysis time significantly. There were 72 samples (41.7% female) collected neonatally, 63 samples (34.9% female) at 6 months, 60 samples (40.0% female) at 12 months and 51 samples (43.1% female) at 24 months. The upper limits for normal values were 233, 615, 136 and 57 microg mg(-1) for infants aged 0, 6, 12 and 24 months, respectively.The Swedish Research Council under Grants 2015-03477, 2010-15062-79050-11, 2015-02434; the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) framework under Grant 340-2013-5867Accepte

Association of Maternal DNA Methylation and Offspring Birthweight

This study aims to evaluate the association of maternal DNA methylation (DNAm) during pregnancy and offspring birthweight. One hundred twenty-two newborn-mother dyads from the Isle of Wight (IOW) cohort were studied to identify differentially methylated cytosine-phosphate-guanine sites (CpGs) in maternal blood associated with offspring birthweight. Peripheral blood samples were drawn from mothers at 22-38 weeks of pregnancy for epigenome-wide DNAm assessment using the Illumina Infinium HumanMethylation450K array. Candidate CpGs were identified using a course of 100 repetitions of a training and testing process with robust regressions. CpGs were considered informative if they showed statistical significance in at least 80% of training and testing samples. Linear mixed models adjusting for covariates were applied to further assess the selected CpGs. The Swedish Born Into Life cohort was used to replicate our findings (n = 33). Eight candidate CpGs corresponding to the genesLMF1,KIF9,KLHL18,DAB1,VAX2,CD207,SCT,SCYL2,DEPDC4,NECAP1, andSFRS3in mothers were identified as statistically significantly associated with their children's birthweight in the IOW cohort and confirmed by linear mixed models after adjusting for covariates. Of these, in the replication cohort, three CpGs (cg01816814, cg23153661, and cg17722033 withpvalues = 0.06, 0.175, and 0.166, respectively) associated with four genes (LMF1,VAX2,CD207, andNECAP1) were marginally significant. Biological pathway analyses of three of the genes revealed cellular processes such as endocytosis (possibly sustaining an adequate maternal-fetal interface) and metabolic processes such as regulation of lipoprotein lipase activity (involved in providing substrates for the developing fetus). Our results contribute to an epigenetic understanding of maternal involvement in offspring birthweight. Measuring DNAm levels of maternal CpGs may in the future serve as a diagnostic tool recognizing mothers at risk for pregnancies ending with altered birthweights.Peer reviewe

DNA methylation differences at birth after conception through ART

STUDY QUESTION: Is there a relation between ART and DNA methylation (DNAm) patterns in cord blood, including any differences between IVF and ICSI? SUMMARY ANSWER: DNAm at 19 CpGs was associated with conception via ART, with no difference found between IVF and ICSI. WHAT IS KNOWN ALREADY: Prior studies on either IVF or ICSI show conflicting outcomes, as both widespread effects on DNAm and highly localized associations have been reported. No study on both IVF and ICSI and genome-wide neonatal DNAm has been performed. STUDY DESIGN, SIZE, DURATION: This was a cross-sectional study comprising 87 infants conceived with IVF or ICSI and 70 conceived following medically unassisted conception. The requirement for inclusion in the study was an understanding of the Swedish language and exclusion was the use of donor gametes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were from the UppstART study, which was recruited from fertility and reproductive health clinics, and the Born into Life cohort, which is recruited from the larger LifeGene study. We measured DNAm from DNA extracted from cord blood collected at birth using a micro-array (450k array). Group differences in DNAm at individual CpG dinucleotides (CpGs) were determined using robust linear models and post-hoc Tukey's tests. MAIN RESULTS AND THE ROLE OF CHANCE: We found no association of ART conception with global methylation levels, imprinted loci and meta-stable epialleles. In contrast, we identify 19 CpGs at which DNAm was associated with being conceived via ART (effect estimates: 0.5-4.9%, PFDR < 0.05), but no difference was found between IVF and ICSI. The associated CpGs map to genes related to brain function/development or genes connected to the plethora of conditions linked to subfertility, but funct

DNA Methylation Trajectories During Pregnancy

There is emerging evidence on DNA methylation (DNAm) variability over time; however, little is known about dynamics of DNAm patterns during pregnancy. We performed an epigenome-wide longitudinal DNAm study of a well-characterized sample of young women from the Swedish Born into Life study, with repeated blood sampling before, during and after pregnancy (n = 21), using the Illumina Infinium MethylationEPIC array. We conducted a replication in the Isle of Wight third-generation birth cohort (n = 27), using the Infinium HumanMethylation450k BeadChip. We identified 196 CpG sites displaying intra-individual longitudinal change in DNAm with a false discovery rate (FDR) P 3 differentially methylated CpGs: HOXB3, AVP, LOC100996291, and MicroRNA 10a. Of 36 CpGs available in the replication cohort, 17 were replicated, all but 2 with the same direction of association (replication P <.05). Biological pathway analysis demonstrated that FDR-significant CpGs belong to genes overrepresented in metabolism-related pathways, such as adipose tissue development, regulation of insulin receptor signaling, and mammary gland fat development. These results contribute to a better understanding of the biological mechanisms underlying important physiological alterations and adaptations for pregnancy and lactation.Peer reviewe

Resandets demokratisering efter 1820

The study deals with the variations of caravan traffic, i.e. the number of departed horses per year in the whole country and in various counties (1855-1906) and in tax charge districts and at single inns (about 1820-1920). Furthermore the variations in sea passenger traffic, i.e. yearly incomes for 66 passenger vessels in domestic traffic during the period of 1860 to 1920. Above this there is information on opening and closing hours per year of Göta Kanal and Trollhätte Kanal and the person kilometers of the railways.Undersökningen tar upp skjutstrafikens variationer, dvs antalet utgångna hästar per år i hela riket och i olika län (1855-1906) samt i fögderier och vid enskilda gästgivargårdar (omkr. 1820-1920). Dessutom behandlas fartygspassagerartrafikens variationer, dvs årliga inkomster för 66 passagerarfartyg i inrikes trafik under perioden 1860-1920. Därutöver finns uppgifter om Göta kanals och Trollhätte kanals öppethållande per år samt järnvägarnas antal personkilometer. Insamlingen har skett med hjälp av regional statistik