Salivary proteome signatures in the early and middle stages of human pregnancy with term birth outcome.
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ABSTRACT:
SUBMITTER: Dey AK
PROVIDER: S-EPMC7229191 | biostudies-literature | 2020 May
REPOSITORIES: biostudies-literature
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Salivary proteome signatures in the early and middle stages of human pregnancy with term birth outcome.
Dey Amit Kumar AK Kumar Bhoj B Singh Abhishek Kumar AK Ranjan Prakash P Thiruvengadam Ramachandran R Desiraju Bapu Koundinya BK Kshetrapal Pallavi P Wadhwa Nitya N Bhatnagar Shinjini S Rashid Faraz F Malakar Dipankar D Salunke Dinakar M DM Maiti Tushar Kanti TK
Scientific reports 20200515 1
The establishment and maintenance of pregnancy in humans proceed through a continuous change of biochemical and biophysical processes. It requires a constant interaction between the fetus and the maternal system. The present prospective study aims to elucidate changes in salivary proteome from the early to middle stages of term pregnancy, and establishing an expressional trajectory for modulated proteins. To date, a comprehensive characterization of the longitudinal salivary proteome in pregnanc ...[more]
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Project description:This prospective study is to find changes in salivary protein expressions from first to early third trimester of pregnancy in normal term birth using SWATH-MS strategy. Saliva at three periods of gestation, 6-13 (V1), 18-21(V2), and 26-29 (V3) weeks from 20 singleton pregnant women were used in a discovery phase. Selected proteins from the discovery study were verified by targeted schedule-MRM (multiple reaction monitoring) experiments in a separate subset of subjects (N=14). Using in-house generated saliva-specific protein library, 65 proteins (q-value<0.1) changed as a function of gestational age.
2020-09-28 | PXD014800 | Pride
Project description:BackgroundSocioeconomic experiences are recognized determinants of health, and recent work has shown that social disadvantages in early life may induce sustained biological changes at molecular level that are detectable later in life. However, the dynamics and persistence of biological embedding of socioeconomic position (SEP) remains vastly unexplored.MethodsUsing the data from the ALSPAC birth cohort, we performed epigenome-wide association studies of DNA methylation changes at three life stages (birth, n = 914; childhood at mean age 7.5 years, n = 973; and adolescence at mean age 15.5 years, n = 974), measured using the Illumina HumanMethylation450 Beadchip, in relation to pregnancy SEP indicators (maternal and paternal education and occupation).ResultsAcross the four early life SEP metrics investigated, only maternal education was associated with methylation levels at birth, and four CpGs mapped to SULF1, GLB1L2 and RPUSD1 genes were identified [false discovery rate (FDR)-corrected P-value <0.05]. No epigenetic signature was found associated with maternal education in child samples, but methylation levels at 20 CpG loci were found significantly associated with maternal education in adolescence. Although no overlap was found between the differentially methylated CpG sites at different ages, we identified two CpG sites at birth and during adolescence which are 219 bp apart in the SULF1 gene that encodes an heparan sulphatase involved in modulation of signalling pathways. Using data from an independent birth cohort, the ENVIRONAGE cohort, we were not able to replicate these findings.ConclusionsTaken together, our results suggest that parental SEP, and particularly maternal education, may influence the offspring's methylome at birth and adolescence.
| S-EPMC6443021 | biostudies-literature
Project description:Ectopic pregnancy (EP) is associated with high maternal morbidity and mortality. Ultrasonography is the only dependable diagnostic tool for confirming an ectopic pregnancy. In view of inadequate early detection methods, women suffer from a high-life risk due to the severity of EP. Early detection of EP using pathological/molecular markers will possibly improve clinical diagnosis and patient management. Salivary proteins contain potential biomarkers for diagnosing and detecting various physiological and/or pathological conditions. Therefore, the present investigation was designed to explore the salivary proteome with special reference to EP. Gel-based protein separation was performed on saliva, followed by identification of proteins using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). Totally, 326 proteins were identified in the salivary samples, among which 101 were found to be specific for ruptured ectopic pregnancy (EPR). Reactome analysis revealed innate immune system, neutrophil degranulation, cell surface interactions at the vascular wall, and FCERI-mediated NF-kB activation as the major pathways to which the salivary proteins identified during EPR are associated. Glutathione-S-transferase omega-1 (GSTO1) is specific for EPR and has been reported as a candidate biomarker in the serum of EPR patients. Therefore, saliva would be a potential source of diagnostic non-invasive protein biomarker(s) for EP. Intensive investigation on the salivary proteins specific to EP can potentially lead to setting up of a panel of candidate biomarkers and developing a non-invasive protein-based diagnostic kit.
| S-EPMC10558548 | biostudies-literature
Project description:BackgroundPeriodontal disease in pregnancy is considered a risk factor for adverse birth outcomes. Periodontal disease has a microbial etiology, however, the current state of knowledge about the subgingival microbiome in pregnancy is not well understood.ObjectiveTo characterize the structure and diversity of the subgingival microbiome in early and late pregnancy and explore relationships between the subgingival microbiome and preterm birth among pregnant Black women.MethodsThis longitudinal descriptive study used 16S rRNA sequencing to profile the subgingival microbiome of 59 Black women and describe microbial ecology using alpha and beta diversity metrics. We also compared microbiome features across early (8-14 weeks) and late (24-30 weeks) gestation overall and according to gestational age at birth outcomes (spontaneous preterm, spontaneous early term, full term).ResultsIn this sample of Black pregnant women, the top twenty bacterial taxa represented in the subgingival microbiome included a spectrum representative of various stages of biofilm progression leading to periodontal disease, including known periopathogens Porphyromonas gingivalis and Tannerella forsythia. Other organisms associated with periodontal disease reflected in the subgingival microbiome included several Prevotella spp., and Campylobacter spp. Measures of alpha or beta diversity did not distinguish the subgingival microbiome of women according to early/late gestation or full term/spontaneous preterm birth; however, alpha diversity differences in late pregnancy between women who spontaneously delivered early term and women who delivered full term were identified. Several taxa were also identified as being differentially abundant according to early/late gestation, and full term/spontaneous early term births.ConclusionsAlthough the composition of the subgingival microbiome is shifted toward complexes associated with periodontal disease, the diversity of the microbiome remains stable throughout pregnancy. Several taxa were identified as being associated with spontaneous early term birth. Two, in particular, are promising targets of further investigation. Depletion of the oral commensal Lautropia mirabilis in early pregnancy and elevated levels of Prevotella melaninogenica in late pregnancy were both associated with spontaneous early term birth.
| S-EPMC9132049 | biostudies-literature
Project description:IntroductionHuman anelloviruses, including torque teno virus (TTV) and torque teno mini virus (TTMV), are ubiquitous in the general population and have no known pathogenicity. We investigated the prevalence and viral load of TTV and TTMV in plasma and saliva over pregnancy, and assessed their association with spontaneous or medically indicated preterm birth.MethodsThis is a secondary analysis of the Measurement of Maternal Stress (MOMS) study, which recruited 744 individuals with singleton pregnancies from 4 US sites (Chicago, Pittsburgh, San Antonio, and rural Pennsylvania). Baseline outpatient visits took place in the second trimester (between 12'0 and 20'6/7 weeks' gestation), and follow-up visits in the third trimester (between 32'0 and 35'6/7 weeks' gestation). In a case-control study design, participants who delivered preterm (<37 weeks) resulting from spontaneous labor and/or preterm premature rupture of membranes ("sPTB") were compared with participants experiencing medically indicated preterm birth ("iPTB"), or delivery at term ("controls"). Plasma and saliva samples obtained during the second and third trimesters were tested for the presence and quantity of TTV and TTMV using real-time PCR. Demographic data were obtained via self-report, and clinical data via medical record review by trained research personnel.ResultsTTV was detected in plasma from 81% (second trimester) and 77% (third trimester) of participants, and in saliva from 64 and 60%. Corresponding detection rates for TTMV were 59 and 41% in plasma, and 35 and 24% in saliva. TTV and TTMV concentrations were similar between matched plasma and saliva samples. TTV prevalence and concentrations were not significantly different between groups (sPTB, iPTB, and controls). However, plasma TTMV in the third trimester was associated with sPTB and earlier gestational age at delivery. The iPTB group was not different from either the sPTB or the control group. In saliva, concentrations of TTV and TTMV were similar among the three groups. Both TTV and TTMV were more prevalent with increasing parity and were more common in Black and Hispanic participants compared to non-Hispanic White participants.ConclusionAnellovirus presence (specifically, TTMV) in the third trimester may be associated with preterm birth. Whether this association is causative remains to be determined.
| S-EPMC10309558 | biostudies-literature
Project description:To examine recurrent preterm birth and early term birth in women's initial and immediately subsequent pregnancies.This retrospective cohort study included 163,889 women who delivered their first and second liveborn singleton neonates between 20 and 44 weeks of gestation in California from 2005 through 2011. Data from hospital discharge records and birth certificates were used for analyses. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression models adjusted for risk factors.Shorter gestational duration in the first pregnancy increased the risk of subsequent preterm birth (both early, before 32 weeks of gestation, and later, from 32 to 36 weeks of gestation) as well as early term birth (37-38 weeks of gestation). Compared with women with a prior term birth, women with a prior early preterm birth (before 32 weeks of gestation) were at the highest risk for a subsequent early preterm birth (58/935 [6.2%] compared with 367/118,505 [0.3%], adjusted OR 23.3, 95% CI 17.2-31.7). Women with a prior early term birth had more than a twofold increased risk for subsequent preterm birth (before 32 weeks of gestation: 171/36,017 [0.5%], adjusted OR 2.0, 95% CI 1.6-2.3; from 32 to 36 weeks of gestation: 2,086/36,017 [6.8%], adjusted OR 3.0, 95% CI 2.9-3.2) or early term birth (13,582/36,017 [37.7%], adjusted OR 2.2, 95% CI 2.2-2.3).Both preterm birth and early term birth are associated with these outcomes in a subsequent pregnancy. Increased clinical attention and research efforts may benefit from a focus on women with a prior early term birth as well as those with prior preterm birth.
| S-EPMC5055875 | biostudies-literature
Project description:ObjectiveTo evaluate the association between the early pregnancy vaginal microbiome and spontaneous preterm birth (sPTB) and early term birth (sETB) among African American women.MethodsVaginal samples collected in early pregnancy (8-14 weeks' gestation) from 436 women enrolled in the Emory University African American Vaginal, Oral, and Gut Microbiome in Pregnancy Study underwent 16S rRNA gene sequencing of the V3-V4 region, taxonomic classification, and community state type (CST) assignment. We compared vaginal CST and abundance of taxa for women whose pregnancy ended in sPTB (N = 44) or sETB (N= 84) to those who delivered full term (N = 231).ResultsNearly half of the women had a vaginal microbiome classified as CST IV (Diverse CST), while one-third had CST III (L. iners dominated) and just 16% had CST I, II, or V (non-iners Lactobacillus dominated). Compared to vaginal CST I, II, or V (non-iners Lactobacillus dominated), both CST III (L. iners dominated) and CST IV (Diverse) were associated with sPTB with an adjusted odds ratio (95% confidence interval) of 4.1 (1.1, infinity) and 7.7 (2.2, infinity), respectively, in multivariate logistic regression. In contrast, no vaginal CST was associated with sETB. The linear decomposition model (LDM) based on amplicon sequence variant (ASV) relative abundance found a significant overall effect of the vaginal microbiome on sPTB (p=0.034) but not sETB (p=0.320), whereas the LDM based on presence/absence of ASV found no overall effect on sPTB (p=0.328) but a significant effect on sETB (p=0.030). In testing for ASV-specific effects, the LDM found that no ASV was significantly associated with sPTB considering either relative abundance or presence/absence data after controlling for multiple comparisons (FDR 10%), although in marginal analysis the relative abundance of Gardnerella vaginalis (p=0.011), non-iners Lactobacillus (p=0.016), and Mobiluncus curtisii (p=0.035) and the presence of Atopobium vaginae (p=0.049), BVAB2 (p=0.024), Dialister microaerophilis (p=0.011), and Prevotella amnii (p=0.044) were associated with sPTB. The LDM identified the higher abundance of 7 ASVs and the presence of 13 ASVs, all commonly residents of the gut, as associated with sETB at FDR < 10%.ConclusionsIn this cohort of African American women, an early pregnancy vaginal CST III or IV was associated with an increased risk of sPTB but not sETB. The relative abundance and presence of distinct taxa within the early pregnancy vaginal microbiome was associated with either sPTB or sETB.
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Project description:Despite decades of attempts to link infectious agents to preterm birth, an exact causative microbe or community of microbes remains elusive. Nonculture 16S ribosomal RNA gene sequencing suggests important racial differences and pregnancy specific changes in the vaginal microbial communities. A recent study examining the association of the vaginal microbiome and preterm birth documented important findings but was performed in a predominantly white cohort. Given the important racial differences in bacterial communities within the vagina as well as persistent racial disparities in preterm birth, it is important to examine cohorts with varied demographic compositions.To characterize vaginal microbial community characteristics in a large, predominantly African-American, longitudinal cohort of pregnant women and test whether particular vaginal microbial community characteristics are associated with the risk for subsequent preterm birth.This is a nested case-control study within a prospective cohort study of women with singleton pregnancies, not on supplemental progesterone, and without cervical cerclage in situ. Serial mid-vaginal swabs were obtained by speculum exam at their routine prenatal visits. Sequencing of the V1V3 region of the 16S rRNA gene was performed on the Roche 454 platform. Alpha diversity community characteristics including richness, Shannon diversity, and evenness as well as beta diversity metrics including Bray Curtis Dissimilarity and specific taxon abundance were compared longitudinally in women who delivered preterm to those who delivered at term.A total of 77 subjects contributed 149 vaginal swabs longitudinally across pregnancy. Participants were predominantly African-American (69%) and had a preterm birth rate of 31%. In subjects with subsequent term delivery, the vaginal microbiome demonstrated stable community richness and Shannon diversity, whereas subjects with subsequent preterm delivery had significantly decreased vaginal richness, diversity, and evenness during pregnancy (P < .01). This change occurred between the first and second trimesters. Within-subject comparisons across pregnancy showed that preterm birth is associated with increased vaginal microbiome instability compared to term birth. No distinct taxa were associated with preterm birth.In a predominantly African-American population, a significant decrease of vaginal microbial community richness and diversity is associated with preterm birth. The timing of this suppression appears early in pregnancy, between the first and second trimesters, suggesting that early gestation may be an ecologically important time for events that ordain subsequent term and preterm birth outcomes.
| S-EPMC5581228 | biostudies-literature
Project description:BackgroundHydroxychloroquine is generally considered safe in pregnancy for the treatment of rheumatic conditions, but studies have been too small to evaluate teratogenicity. Quantifying the risk of congenital malformations associated with early pregnancy exposure to hydroxychloroquine is important in both the context of its ongoing use for rheumatological disorders and its potential future use for coronavirus disease 2019 prophylaxis, for which a number of clinical trials are ongoing despite initial trials for coronavirus disease 2019 treatment having been negative.ObjectiveThe study objective was to evaluate the risk of major congenital malformations associated with exposure to hydroxychloroquine during the first trimester of pregnancy, the period of organogenesis.Study designWe performed a population-based cohort study nested in the Medicaid Analytic eXtract (MAX, 2000-2014) and IBM MarketScan Research Database (MarketScan, 2003-2015). The source cohort included 2045 hydroxychloroquine-exposed pregnancies and 3,198,589 pregnancies not exposed to hydroxychloroquine continuously enrolled in their respective insurance program for 3 months before the last menstrual period through at least 1 month after delivery; infants were enrolled for at least 3 months after birth. We compared the risk of congenital malformations in women using hydroxychloroquine during the first trimester of pregnancy with that of those not using hydroxychloroquine, restricting the cohort to women with rheumatic disorders and using propensity score matching to control for indication, demographics, medical comorbidities, and concomitant medications (1867 hydroxychloroquine-exposed pregnancies and 19,080 pregnancies not exposed to hydroxychloroquine). The outcomes considered included major congenital malformations diagnosed during the first 90 days after delivery and specific malformation types for which there were at least 5 exposed events: oral cleft, cardiac, respiratory, gastrointestinal, genital, urinary, musculoskeletal, and limb defects.ResultsOverall, 54.8 per 1000 infants exposed to hydroxychloroquine were born with a major congenital malformation versus 35.3 per 1000 unexposed infants, corresponding to an unadjusted relative risk of 1.51 (95% confidence interval, 1.27-1.81). Patient characteristics were balanced in the restricted, propensity score-matched cohort. The adjusted relative risk was 1.26 (95% confidence interval, 1.04-1.54); it was 1.33 (95% confidence interval, 1.08-1.65) for a daily dose of ≥400 mg and 0.95 (95% confidence interval, 0.60-1.50) for a daily dose of <400 mg. Among the different malformation groups considered, more substantial increases in the risk of oral clefts, respiratory anomalies, and urinary defects were observed, although estimates were imprecise. No pattern of malformation was identified.ConclusionOur findings suggest a small increase in the risk of malformations associated with first-trimester hydroxychloroquine use. For most patients with autoimmune rheumatic disorders, the benefits of treatment during pregnancy will likely outweigh this risk. If hydroxychloroquine were shown to be effective for coronavirus disease 2019 prophylaxis in ongoing trials, the risk of malformations would need to be balanced against such benefits.
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Project description:Background:Different oscillations of brain networks could carry different dimensions of brain integration. We aimed to investigate oscillation-specific nodal alterations in patients with Parkinson's disease (PD) across early stage to middle stage by using graph theory-based analysis. Methods:Eighty-eight PD patients including 39 PD patients in the early stage (EPD) and 49 patients in the middle stage (MPD) and 36 controls were recruited in the present study. Graph theory-based network analyses from three oscillation frequencies (slow-5: 0.01-0.027?Hz; slow-4: 0.027-0.073?Hz; slow-3: 0.073-0.198?Hz) were analyzed. Nodal metrics (e.g. nodal degree centrality, betweenness centrality and nodal efficiency) were calculated. Results:Our results showed that (1) a divergent effect of oscillation frequencies on nodal metrics, especially on nodal degree centrality and nodal efficiency, that the anteroventral neocortex and subcortex had high nodal metrics within low oscillation frequencies while the posterolateral neocortex had high values within the relative high oscillation frequency was observed, which visually showed that network was perturbed in PD; (2) PD patients in early stage relatively preserved nodal properties while MPD patients showed widespread abnormalities, which was consistently detected within all three oscillation frequencies; (3) the involvement of basal ganglia could be specifically observed within slow-5 oscillation frequency in MPD patients; (4) logistic regression and receiver operating characteristic curve analyses demonstrated that some of those oscillation-specific nodal alterations had the ability to well discriminate PD patients from controls or MPD from EPD patients at the individual level; (5) occipital disruption within high frequency (slow-3) made a significant influence on motor impairment which was dominated by akinesia and rigidity. Conclusions:Coupling various oscillations could provide potentially useful information for large-scale network and progressive oscillation-specific nodal alterations were observed in PD patients across early to middle stages.
| S-EPMC6857322 | biostudies-literature