Project description:Polycystic ovary syndrome (PCOS) is the most common endocrinological disorder of fertile-aged women. PCOS has been associated with adverse pregnancy outcomes and abnormalities of the placenta. By taking a quantitative label-free quantitative proteomics approach we set out to investigate if changes in the plasma proteome of pregnant women with PCOS could elucidate the mechanisms behind the pathologies observed in PCOS pregnancies. We have performed label-free quantitative proteomics on plasma samples from pregnant women with PCOS at term (n=14) and plasma samples from pregnant control women (n = 23) matched for age, gestational length and BMI. The samples are derived from BASIC pregnancy cohort from Uppsala, Sweden. A total of 169 proteins with two or more unique peptides were identified.
Project description:The onset of menopause is accompanied by a dramatic increase in reported symptoms of vaginal dryness, soreness, irritation or itching, pain with intercourse and bleeding after intercourse. Collectively these affect 25-50% of women of post-menopausal age and significantly impact their quality of life. To examine how gene expression differs between these groups, surface vaginal epithelial cells were collected from postmenopausal women suffering from vaginal dryness and appropriate controls not suffering from dryness. Affymetrix GeneChip Human 1.0 ST microarrays were performed on RNA isolated from ten participants.
Project description:The onset of menopause is accompanied by a dramatic increase in reported symptoms of vaginal dryness, soreness, irritation or itching, pain with intercourse and bleeding after intercourse. Collectively these affect 25-50% of women of post-menopausal age and significantly impact their quality of life. To examine how gene expression differs between these groups, surface vaginal epithelial cells were collected from postmenopausal women suffering from vaginal dryness and appropriate controls not suffering from dryness. Affymetrix GeneChip Human 1.0 ST microarrays were performed on RNA isolated from ten participants. Suitable RNA was extracted from ten participants which were classified into two groups, the dryness and control groups, based on diagnosis of dryness by a nurse during gynecoligical examination.
Project description:Spontaneous preterm birth (sPTB) is a leading cause of maternal and neonatal morbidity and mortality, yet its prevention and early risk stratification are limited. Previous investigations have suggested that vaginal microbes and metabolites may be implicated in sPTB. Here we performed untargeted metabolomics on 232 second-trimester vaginal samples, 80 from pregnancies ending preterm. We find multiple associations between vaginal metabolites and subsequent preterm birth, and propose that several of these metabolites, including diethanolamine and ethyl glucoside, are exogenous. We observe associations between the metabolome and microbiome profiles previously obtained using 16S ribosomal RNA amplicon sequencing, including correlations between bacteria considered suboptimal, such as Gardnerella vaginalis, and metabolites enriched in term pregnancies, such as tyramine. We investigate these associations using metabolic models. We use machine learning models to predict sPTB risk from metabolite levels, weeks to months before birth, with good accuracy (area under receiver operating characteristic curve of 0.78). These models, which we validate using two external cohorts, are more accurate than microbiome-based and maternal covariates-based models (area under receiver operating characteristic curve of 0.55-0.59). Our results demonstrate the potential of vaginal metabolites as early biomarkers of sPTB and highlight exogenous exposures as potential risk factors for prematurity.
Project description:This study investigates the dynamic alterations in high vaginal fluid (HVF) proteome and its correlation with physiological changes during progression of term pregnancy. The HVF samples were collected at three time points as defined as V1 (6-12 weeks), V2 (18-20 weeks) and V3 (26-28 weeks) and SWATH-MS strategy were applied to profile changes in protein expression at early and middle stage of pregnancy. Using in-house generated HVF-specific protein library, 61 proteins (>1.5 fold at V2/V1 or V3/V1, q-value <0.05) changed as a function of gestational age. The stage-specific expression pattern of these proteins was mainly associated with the biology of cervical remolding, fetal development and microbial defense.
Project description:This study investigates the dynamic alterations in high vaginal fluid (HVF) proteome and its correlation with physiological changes during progression of term pregnancy. The HVF samples were collected at three time points as defined as V1 (6-12 weeks), V2 (18-20 weeks) and V3 (26-28 weeks) and SWATH-MS strategy were applied to profile changes in protein expression at early and middle stage of pregnancy. Using in-house generated HVF-specific protein library, 61 proteins (>1.5 fold at V2/V1 or V3/V1, q-value <0.05) changed as a function of gestational age. The stage-specific expression pattern of these proteins was mainly associated with the biology of cervical remolding, fetal development and microbial defense.
Project description:Pregnancy in Sickle Cell Disease (SCD) women is associated to increased risk of clinical and obstetrical complications. Placentas from SCD pregnancies can present increased abnormal findings, which may lead to placental insufficiency, favoring adverse perinatal outcome. These placental abnormalities are well known and reported, however little is known about the molecular mechanisms, such as epigenetics. Thus, our aim was to evaluate the DNA methylation profile in placentas from women with SCD (HbSS and HbSC genotypes), compared to uncomplicated controls (HbAA). We included in this study 11 pregnant women with HbSS, 11 with HbSC and 21 with HbAA genotypes. Illumina Methylation EPIC BeadChip was used to assess the whole placental DNA methylation. Pyrosequencing was used for array data validation and qRT-PCR was applied for gene expression analysis. Our results showed high frequency of hypermethylated CpGs sites in HbSS and HbSC groups with 73.5% and 76.2% respectively, when compared with the control group. Differentially methylated regions (DMRs) also showed an increased hypermethylation status for the HbSS (89%) and HbSC (86%) groups, when compared with the control group methylation data. DMRs were selected for methylation validation (4 DMRs-HbSS and 3 DMRs the HbSC groups) and after analyses three were validated in the HbSS group, and none in the HbSC group. The gene expression analysis showed differential expression for the PTGFR (-2.97-fold) and GPR56 (3.0-fold) genes in the HbSS group, and for the SPOCK1 (-2.40-fold) and ADCY4 (1.80-fold) genes in the HbSC group. Taken together, these data strongly suggest that SCD (HbSS and HbSC genotypes) can alter placental DNA methylation and lead to gene expression changes. These changes possibly contribute to abnormal placental development and could impact in the clinical course, especially for the fetus, possibly leading to increased risk of abortion, fetal growth restriction (FGR), stillbirth, small for gestational age newborns and prematurity.