Publications
243 results found
Cook J, Bennett P, Kim SH, et al., 2019, First trimester circulating MicroRNA biomarkers predictive of subsequentpreterm delivery and cervical shortening, Scientific Reports, Vol: 9, ISSN: 2045-2322
Preterm birth (PTB) is the leading cause of infant death and disability worldwide. The onset of preterm uterine contractions is preceded by asymptomatic cervical remodelling and ripening, which can be seen on trans-vaginal ultrasound as cervical shortening. This study aimed to identify plasma miRNA biomarkers that predict preterm birth and/or cervical shortening. We collected serial plasma samples from pregnant women prospectively from 12 to 22 weeks gestation. The nCounter miRNA assay was used to identify differentially expressed miRNAs associated with spontaneous PTB and/or cervical shortening (n = 16 term no short, n = 13 preterm, n = 24 short). Predictive values of the miRNA biomarkers were confirmed in an independent validation cohort consisting of 96 women who delivered at term, 14 preterm and 21 early cervical shortening at <20 weeks gestation. Nine miRNAs (hsa-let-7a-5p, hsa-miR-374a-5p, hsa-miR-15b-5p, hsa-miR-19b-3p, hsa-miR-23a-3p, hsa-miR-93-5p, hsa-miR-150-5p, hsa-miR-185-5p and hsa-miR-191-5p) were differentially expressed (P < 0.001) in women subsequently experiencing PTB or cervical shortening. Hsa-miR-150-5p had the strongest ability to predict PTB (AUC = 0.8725) and cervical shortening (AUC = 0.8514). Plasma miRNAs in the first trimester can predict PTB and cervical shortening in women at risk of preterm delivery. This is a key period in pregnancy when early identification of PTB risk allows time to deliver outcome-modifying interventions.
Mowla S, Xie J, Bennett P, et al., 2019, Characterisation of Vaginal Cytokine Expression During ART: A Cohort Study., 66th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 256A-256A, ISSN: 1933-7191
Hanton FD, Lee Y, Gunstone H, et al., 2019, The Role of Lactate Acidification on Inflammatory Pathway Activation in Vaginal Epithelial Cells., 66th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 345A-345A, ISSN: 1933-7191
Chan D, Lee YS, Ahmed S, et al., 2019, The Local and Systemic Immune Response in Preterm and Term Pregnancies and Their Association with the Vaginal Microbiota., 66th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 75A-75A, ISSN: 1933-7191
Rasheed ZBM, San Martin CR, Sullivan MHF, et al., 2019, The Placenta Exhibits Selective Immune Response in an In Vitro Model of Haematogenous Multi- Pathogen Induced Preterm Labour., 66th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 74A-74A, ISSN: 1933-7191
Chan D, Lee YS, Teoh TG, et al., 2019, Maternal Gut Microbial-Immune Interactions during Healthy Pregnancy., 66th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 121A-121A, ISSN: 1933-7191
Kim SH, MacIntyre DA, Bennett PR, et al., 2019, The Effects of Blood Storage on Plasma miRNA Expression Profiles., 66th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 285A-286A, ISSN: 1933-7191
Channon RB, Pavagada S, Chang JYH, et al., 2019, Point-of-care nucleic Acid sensors via paper-based oligonucleotide-templated reactions, Pages: 815-816
This paper describes a new and inexpensive approach for specific sensing of endogenous concentrations of miRNAs extracted from blood, based on a fluorogenic oligonucleotide templated reaction (OTR) on a lateral flow assay (LFA). Our method is then applied to develop the first early screening test for Preterm birth.
Pruski P, Lewis H, Lee Y, et al., 2018, Assessment of microbiota:host interactions at the vaginal mucosa interface, Methods, Vol: 149, Pages: 74-84, ISSN: 1046-2023
There is increasing appreciation of the role that vaginal microbiota play in health and disease throughout a woman’s lifespan. This has been driven partly by molecular techniques that enable detailed identification and characterisation of microbial community structures. However, these methods do not enable assessment of the biochemical and immunological interactions between host and vaginal microbiota involved in pathophysiology. This review examines our current knowledge of the relationships that exist between vaginal microbiota and the host at the level of the vaginal mucosal interface. We also consider methodological approaches to microbiomic, immunologic and metabolic profiling that permit assessment of these interactions. Integration of information derived from these platforms brings the potential for biomarker discovery, disease risk stratification and improved understanding of the mechanisms regulating vaginal microbial community dynamics in health and disease.
Foo F, Mahendru A, Masini G, et al., 2018, Association between prepregnancy cardiovascular function and subsequent preeclampsia or fetal growth restriction, Hypertension, Vol: 72, Pages: 442-450, ISSN: 0194-911X
Preeclampsia and fetal growth restriction during pregnancy are associated with increased risk of maternal cardiovascular disease later in life. It is unclear whether this association is causal or driven by similar antecedent risk factors. Clarification requires recruitment before conception which is methodologically difficult with high attrition rates and loss of outcome numbers to nonconception/miscarriage. Few prospective studies have, therefore, been adequately powered to address these questions. We recruited 530 healthy women (mean age: 35.0 years) intending to conceive and assessed cardiac output, cardiac index, stroke volume, total peripheral resistance, mean arterial pressure, and heart rate before pregnancy. Participants were followed to completion of subsequent pregnancy with repeat longitudinal assessments. Of 356 spontaneously conceived pregnancies, 15 (4.2%) were affected by preeclampsia and fetal growth restriction. Women who subsequently developed preeclampsia/fetal growth restriction had lower preconception cardiac output (4.9 versus 5.8 L/min; P=0.002) and cardiac index (2.9 versus 3.3 L/min per meter2; P=0.031) while mean arterial pressure (87.1 versus 82.3 mm Hg; P=0.05) and total peripheral resistance (1396.4 versus 1156.1 dynes sec cm−5; P<0.001) were higher. Longitudinal trajectories for cardiac output and total peripheral resistance were similar between affected and healthy pregnancies, but the former group showed a more exaggerated fall in mean arterial pressure in the first trimester, followed by a steeper rise and a steeper fall to postpartum values. Significant relationships were observed between cardiac output, total peripheral resistance, and mean arterial pressure and gestational epoch. We conclude that in healthy women, an altered prepregnancy hemodynamic phenotype is associated with the subsequent development of preeclampsia/fetal growth restriction.
Chan DCY, Lee YS, Bura S, et al., 2018, The vaginal microbiota and the adaptive immune system in pregnant and nonpregnant women, Publisher: WILEY, Pages: E32-E32, ISSN: 1470-0328
Lewis H, Brown R, Kindinger L, et al., 2018, Rapid mucosal metabolome profiling by desorption electrospray ionization mass spectrometry for prediction of preterm prelabour rupture of membranes, Publisher: WILEY, Pages: E33-E33, ISSN: 1470-0328
Chan DCY, Lee YS, Bura S, et al., 2018, Recognition of vaginal microbiota by the adaptive maternal immune system, 65th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: Sage, Pages: 116A-116A, ISSN: 1933-7191
Lewis H, Pruski P, Brown R, et al., 2018, Rapid mucosal metabolome profiling by desorption electrospray ionization MS (DESI-MS) for prediction of preterm pre-labour rupture of membranes (PPROM), RCOG World Congress 2018, Publisher: Wiley, Pages: 24-24, ISSN: 1470-0328
Rasheed ZBM, Rai RK, Lee YS, et al., 2018, The effect of TLR3 priming on TLR2, 4 and 6 induced activation of NF-kappa band AP-1 in human myometrium, amnion and vaginal epithelial cells, 65th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: Sage, Pages: 188A-188A, ISSN: 1933-7191
Kim SH, Binkhamis R, Cook JR, et al., 2018, A pilot study of circulating miRNAs as potential biomarkers for small-for-gestational-age births, 65th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: Sage, Pages: 282A-282A, ISSN: 1933-7191
Rasheed ZBM, Rai RK, Anucha E, et al., 2018, TLR3 priming increases TLR4-and TLR6-mediated pro-inflammatory cytokine production in amniocytes, myocytes and vaginal epithelial cells, 65th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: Sage, Pages: 258A-258A, ISSN: 1933-7191
Kim SH, MacIntyre DA, Sykes L, et al., 2018, Comparing the Levels of miRNA Expression in Plasma from Blood Collected Using EDTA and Heparin Tubes, and Heparinase-Treated Plasma., 65th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 315A-315A, ISSN: 1933-7191
Brown RG, Chan D, Lee Y, et al., 2018, Rescue Cervical Cerclage is Associated with Good Neonatal Outcomes in Asymptomatic Women Who Are Not Colonised by <i>Gardnerella Vaginalis</i>., 65th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 112A-112A, ISSN: 1933-7191
Lewis HV, Pruski P, Brown RG, et al., 2018, Rapid Mucosal Metabolome Profiling by Desorption Electrospray Ionization MS (DESI-MS) for Prediction of Preterm Pre-Labour Rupture of Membranes (PPROM)., 65th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 65A-65A, ISSN: 1933-7191
Hanton F, Foley J, Lee YS, et al., 2018, Impact of Lactate Acidification on Inflammatory Pathway Activation in Vaginal Epithelial Cells., 65th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 115A-116A, ISSN: 1933-7191
MacIntyre DA, Brown R, Marchesi J, et al., 2018, Vaginal dysbiosis increases risk of preterm fetal membrane rupture, neonatal sepsis and is exacerbated by erythromycin, BMC Medicine, Vol: 16, ISSN: 1741-7015
Background: Preterm prelabour rupture of the fetal membranes (PPROM) precedes 30% of preterm births and is a risk factor for early onset neonatal sepsis. As PPROM is strongly associated with ascending vaginal infection prophylactic antibiotics are widely used. The evolution of vaginal microbiota composition associated with PPROM and the impact of antibiotics on bacterial composition is unknown. Methods: We prospectively assessed vaginal microbiota prior to and following PPROM using MiSeq-based sequencing of 16S rRNA gene amplicons and examined the impact of erythromycin prophylaxis on bacterial load and community structures.Results: In contrast to pregnancies delivering at term, vaginal dysbiosis characterised by Lactobacillus spp. depletion, was present prior to the rupture of fetal membranes in approximately a third of cases (0% versus 27%, P= 0.026) and persisted following membrane rupture (31%, P= 0.005). Vaginal dysbiosis was exacerbated by erythromycin treatment (47%, P= 0.00009) particularly in women initially colonised by Lactobacillus species. Lactobacillus depletion and increased relative abundance of Sneathia spp. was associated with subsequent funisitis and early onset neonatal sepsis. Conclusions:Our data show that vaginal microbiota composition is a risk-factor for subsequent PPROM and is associated with adverse short-term maternal and neonatal outcomes. This highlights vaginal microbiota as a potentially modifiable antenatal risk factor for PPROM and suggests that routine use of erythromycin for PPROM be re-examined.
Cacciatore S, Tenori L, Luchinat C, et al., 2017, KODAMA: an R package for knowledge discovery and data mining, Bioinformatics, Vol: 33, Pages: 621-623, ISSN: 1367-4803
Summary: KODAMA, a novel learning algorithm for unsuper-vised feature extraction, is specifically designed for analysing noisy and high-dimensional data sets. Here we present an R package of the algorithm with additional functions that allow improved interpretation of high-dimensional data. The pack-age requires no additional software and runs on all major plat-forms.Availability and Implementation: KODAMA is freely available from the R archive CRAN (http://cran.r-project.org). The soft-ware is distributed under the GNU General Public License (ver-sion 3 or later).
MacIntyre DA, Sykes L, Bennett P, 2017, The human female urogenital microbiome: complexity in normality, Emerging Topics in Life Sciences, Vol: 1, Pages: 363-372, ISSN: 2397-8554
Microbial communities of the urogenital tract have long been recognised to play an important role in disease states. A revolution in methodological approaches is permitting the assessment of complex urogenital tract microbiota–host interactions and the metabolic and protein milieu of the mucosal interface. There is now great potential for significant advances in biomarker discovery and disease risk stratification, and for the elucidation of mechanisms underpinning the microbial community dynamics involved in urogenital tract pathology. Microbiota–host interactions in the female genital tract have a particular significance, because unlike in the male, there is direct communication between the external genitalia, the uterus and the peritoneal cavity. This review examines the microbial community composition at differing sites of the female urogenital tract and its relationship with health and disease. Key factors involved in the modulation of vaginal microbiome stability and structure, such as endocrine, immune and inflammatory pathways, are considered in the context of a woman's life cycle and disease pathogenesis.
Edey LF, Georgiou H, O'Dea KP, et al., 2017, Progesterone, the maternal immune system and the onset of parturition in the mouse, Biology of Reproduction, Vol: 98, Pages: 376-395, ISSN: 1529-7268
The role of progesterone (P4) in the regulation of the local (uterine) and systemic innate immune system, myometrial expression of connexin 43 (Cx-43) and cyclooxygenase 2 (COX-2) and the onset of parturition was examined in: 1) naïve mice delivering at term; 2) E16 mice treated with RU486 (P4-antagonist) to induce preterm parturition; and 3) in mice treated with P4 to prevent term parturition.In naïve mice, myometrial neutrophil and monocyte numbers peaked at E18 and declined with the onset of parturition. In contrast, circulating monocytes did not change and although neutrophils were increased with pregnancy, they did not change across gestation. The myometrial mRNA and protein levels of most chemokines/cytokines, Cx-43 and COX-2 increased with, but not before, parturition.With RU486-induced parturition, myometrial and systemic neutrophil numbers increased before and myometrial monocyte numbers increased with parturition only. Myometrial chemokine/cytokine mRNA abundance increased with parturition, but protein levels peaked earlier at between 4.5 and 9h post RU486. Cx-43, but not COX-2, mRNA expression and protein levels increased prior to the onset of parturition.In mice treated with P4, the gestation-linked increase in myometrial monocyte, but not neutrophil, numbers was prevented and expression of Cx-43 and COX-2 was reduced. On E20 of P4 supplementation, myometrial chemokine/cytokine and leukocyte numbers, but not Cx-43 and COX-2 expression, increased.These data show that during pregnancy P4 controls myometrial monocyte infiltration, cytokine and prolabour factor synthesis via mRNA dependent and independent mechanisms and, with prolonged P4 supplementation, P4 action is repressed resulting in increased myometrial inflammation.
Mitra A, MacIntyre D, Lee Y, et al., 2017, THE VAGINAL MICROBIOTA AFTER EXCISIONAL TREATMENT FOR CERVICAL INTRAEPITHELIAL NEOPLASIA, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 979-979, ISSN: 1048-891X
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Bray R, Cacciatore S, Jimenez B, et al., 2017, Urinary metabolic phenotyping of women with lower urinary tract symptoms, Journal of Proteome Research, Vol: 16, Pages: 4208-4216, ISSN: 1535-3893
Lower urinary tract symptoms (LUTS), including urinary incontinence, urgency and nocturia, affect approximately half of women worldwide. Current diagnostic methods for LUTS are invasive and costly, while available treatments are limited by side effects leading to poor patient compliance. In this study, we aimed to identify urine metabolic signatures associated with LUTS using proton nuclear magnetic resonance (1H NMR) spectroscopy. A total of 214 urine samples were collected from women attending tertiary urogynecology clinics (cases; n = 176) and healthy control women attending general gynecology clinics (n = 36). Despite high variation in the urine metabolome across the cohort, associations between urine metabolic profiles and BMI, parity, overactive bladder syndrome, frequency, straining, and bladder storage were identified using KODAMA (knowledge discovery by accuracy maximization). Four distinct urinary metabotypes were identified, one of which was associated with increased urinary frequency and low BMI. Urine from these patients was characterized by increased levels of isoleucine and decreased levels of hippurate. Our study suggests that metabolic profiling of urine samples from LUTS patients offers the potential to identify differences in underlying etiology, which may permit stratification of patient populations and the design of more personalized treatment strategies.
Mitra A, Mahajan V, Macintyre D, et al., 2017, Comparison of vaginal microbiota sampling techniques: cytobrush versus swab, Scientific Reports, Vol: 7, ISSN: 2045-2322
Evidence suggests the vaginal microbiota (VM) may influence risk of persistent Human Papillomavirus (HPV) infection and cervical carcinogenesis. Established cytology biobanks, typically collected with a cytobrush, constitute a unique resource to study such associations longitudinally. It is plausible that compared to rayon swabs; the most commonly used sampling devices, cytobrushes may disrupt biofilms leading to variation in VM composition. Cervico-vaginal samples were collected with cytobrush and rayon swabs from 30 women with high-grade cervical precancer. Quantitative PCR was used to compare bacterial load and Illumina MiSeq sequencing of the V1-V3 regions of the 16S rRNA gene used to compare VM composition. Cytobrushes collected a higher total bacterial load. Relative abundance of bacterial species was highly comparable between sampling devices (R2 = 0.993). However, in women with a Lactobacillus-depleted, high-diversity VM, significantly less correlation in relative species abundance was observed between devices when compared to those with a Lactobacillus species-dominant VM (p = 0.0049). Cytobrush and swab sampling provide a comparable VM composition. In a small proportion of cases the cytobrush was able to detect underlying high-diversity community structure, not realized with swab sampling. This study highlights the need to consider sampling devices as potential confounders when comparing multiple studies and datasets.
Mitra A, MacIntyre D, Lai J, et al., 2017, The impact of excisional treatment for cervical intraepithelial neoplasia on the vaginal microbiota, 64th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: Sage Publications, Pages: 89A-89A, ISSN: 1071-5576
Brown RG, Lee YS, Smith A, et al., 2017, Vaginal Dysbiosis Increases Risk of Preterm Membrane Rupture, Funisitis and Neonatal Sepsis., 64th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 64A-64A, ISSN: 1933-7191
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