Publications
465 results found
Cook JR, MacIntyre DA, Samara E, et al., 2015, Exogenous oxytocin modulates human myometrial microRNAs, American Journal of Obstetrics and Gynecology, Vol: 213, Pages: 65.e1-65.e9, ISSN: 0002-9378
Objective: MicroRNAs (miRNAs) play a modulatory role in pathways that lead to labor onset, although oxytocin is known to modulate gene expression within the myometrium. We aimed to identify miRNAs whose expression is regulated by oxytocin in pregnant human myometrium. Study Design: Myometrial miRNA expression profiles were compared between samples collected from women at term before the onset of labor (no labor; n= 8) and after labor onset after early exogenous oxytocin treatment (n= 8). Multivariate modelling was used to assess differences in miRNA profiles. Biologic validation was undertaken on 3 independent patient cohorts (no labor, n= 10; labor induced with oxytocin, n= 8; and spontaneous labor with no oxytocin treatment, n= 10). Invitro studies that used primary myocytes were undertaken to assess target miRNA expression after oxytocin treatment. Target genes of candidate miRNAs were identified in silico and cross-referenced with genes that are known to be associated with labor or expressed in myometrium. Results: In total, 1309 miRNAs were analyzed by microarray, of which 494 were detected in human myometrium. Multivariate modeling identified 12 target miRNAs the differential expression of which was most responsible for the observed separation of the 2 patient populations in the primary discovery cohorts. Biologic validation in the independent secondary sample cohorts showed that oxytocin independently regulated 5 miRNAs (hsa-miR-146b-3p, hsa-miR-196b-3p, hsa-miR-223-3p, hsa-miR-873-5p, and hsa-miR-876-5p). Additionally, hsa-miR-146b-3p was increased both in labor that was induced with oxytocin and in myometrium from spontaneous labor with no oxytocin treatment compared with no labor samples. Four of the validated miRNAs (hsa-miR-146a-5p, hsa-miR-146b-3p, hsa-miR-196b-3p, and hsa-miR-876-5p) were expressed in primary human myocytes; oxytocin treatment of these cells replicated the directional changes that were observed invivo. Conclusion: Oxytocin alters the e
Cook J, MacIntyre D, Samara E, et al., 2015, Exogenous oxytocin modulates human myometrial microRNAs, Publisher: Elsevier, Pages: E1-E9, ISSN: 1097-6868
Karda R, Delhove JMKM, Buckley SMK, et al., 2015, Generation of Light-Emitting Somatic-Transgenic Mice for Disease Modelling of Hypoxic Ischaemic Encephalopathy, REPRODUCTIVE SCIENCES, Vol: 22, Pages: 174A-174A, ISSN: 1933-7191
Shah N, Imami N, Johnson MR, 2015, Changes in T Cell, Dendritic Cell and NK Cell Phenotype, and T Cell Function From Mid To Late Pregnancy Indicate a Shift From Immune Tolerance To Increased Immune Activation., REPRODUCTIVE SCIENCES, Vol: 22, Pages: 279A-279A, ISSN: 1933-7191
Zollner J, Howe L, Leiper J, et al., 2015, Cecal Ligation and Puncture in Pregnancy, REPRODUCTIVE SCIENCES, Vol: 22, Pages: 274A-275A, ISSN: 1933-7191
Howe L, Zollner J, Leiper J, et al., 2015, Elucidation of the Role of the DDAH/ADMA/NO Axis in Pregnancy-Related Haemodynamic Adaptation, REPRODUCTIVE SCIENCES, Vol: 22, Pages: 184A-184A, ISSN: 1933-7191
Howe L, Zollner J, Leiper J, et al., 2015, Protection From Endotoxin-Induced Hypotension in Pregnancy: Attenuation By CCR2 Deficiency or Pharmacological Inhibition, REPRODUCTIVE SCIENCES, Vol: 22, Pages: 65A-65A, ISSN: 1933-7191
Zollner J, Howe L, Leiper J, et al., 2015, Elucidation of the Role of Estrogen on Cardiovascular Function in a Model of Endotoxaemia, REPRODUCTIVE SCIENCES, Vol: 22, Pages: 274A-274A, ISSN: 1933-7191
Cook JR, MacIntyre DA, Samara E, et al., 2015, Oxytocin Modulates a Unique Set of Human Myometrial MicroRNAs, Publisher: SAGE PUBLICATIONS INC, Pages: 67A-67A, ISSN: 1933-7191
Das A, Sooranna SR, Johnson MR, 2015, Stretch-Induced Changes in the Human Amnion., REPRODUCTIVE SCIENCES, Vol: 22, Pages: 325A-325A, ISSN: 1933-7191
Yulia A, Sooranna SR, Johnson MR, 2015, The Effect of cAMP Elevating Agents on cAMP Related Genes During Gestation in Human Myometrium, REPRODUCTIVE SCIENCES, Vol: 22, Pages: 142A-142A, ISSN: 1933-7191
Georgiou EX, Lai PF, Yulia A, et al., 2015, Progesterone Repression of IL-1β-Driven COX-2 Expression in Myometrial Explant Cultures, Publisher: SAGE PUBLICATIONS INC, Pages: 134A-134A, ISSN: 1933-7191
Zheng X, Sooranna SR, Ma D, et al., 2015, The Effect of Different Fat Contents of Maternal Diets on Mice Which Suffered Perinatal Asphyxia, REPRODUCTIVE SCIENCES, Vol: 22, Pages: 365A-365A, ISSN: 1933-7191
Lei K, Sooranna SR, Johnson MR, 2015, P4 Plays Its Anti-inflammatory Role Primarily Via GR and the Inhibition of AP-1 in Human Myometrial Cells, REPRODUCTIVE SCIENCES, Vol: 22, Pages: 136A-136A, ISSN: 1933-7191
Yulia A, Georgiou EX, Lei K, et al., 2015, The Effects of Combinations of cAMP and Progesterone on Progesterone Responsive Genes in Term Human Myometrium, REPRODUCTIVE SCIENCES, Vol: 22, Pages: 142A-142A, ISSN: 1933-7191
Singh N, Herbert BR, Sooranna SR, et al., 2015, Differences in Inflammatory Chemokine/Cytokine Expression Between Different Stages of Term Labour and Clinical Subtypes of Preterm Labour, REPRODUCTIVE SCIENCES, Vol: 22, Pages: 140A-140A, ISSN: 1933-7191
Lai PF, Tribe RM, Johnson MR, 2015, Sustained Presence of Progesterone Reduces Spontaneous Contractility Enhanced By Prolonged Exposure To 8-bromo-cAMP., Publisher: SAGE PUBLICATIONS INC, Pages: 334A-334A, ISSN: 1933-7191
Migale R, MacIntyre DA, Lee YS, et al., 2015, Mouse Myometrial Transcriptome Analysis By RNAseq Shows Inflammation Is a Side-Effect, Not a Requisite, for Labor, Publisher: SAGE PUBLICATIONS INC, Pages: 66A-66A, ISSN: 1933-7191
Ruys TPE, Maggioni A, Johnson MR, et al., 2014, Cardiac medication during pregnancy, data from the ROPAC, INTERNATIONAL JOURNAL OF CARDIOLOGY, Vol: 177, Pages: 124-128, ISSN: 0167-5273
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- Citations: 71
Taggart MJ, Hume R, Lartey J, et al., 2014, Cardiac remodelling during pregnancy: whither the guinea pig?, CARDIOVASCULAR RESEARCH, Vol: 104, Pages: 226-227, ISSN: 0008-6363
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- Citations: 4
Salam AMF, Hall R, Johnson M, et al., 2014, Predictors of atrial fibrillation during pregnancy in patients with heart disease; analysis from the ROPAC registry, Annual Meeting of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 575-575, ISSN: 0195-668X
Salam AMF, Hall R, Johnson MR, et al., 2014, Impact of atrial fibrillation/flutter during pregnancy on maternal mortality in patients with heart disease; analysis from the ROPAC registry, Annual Meeting of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 574-574, ISSN: 0195-668X
Salam AMF, Hall R, Johnson M, et al., 2014, Impact of atrial fibrillation/flutter during pregnancy in patients with heart disease on fetal outcomes; analysis from the ROPAC registry, Annual Meeting of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 576-577, ISSN: 0195-668X
Yulia A, Johnson MR, 2014, Myometrial oxytocin receptor expression and intracellular pathways., Minerva Ginecol, Vol: 66, Pages: 267-280
Oxytocin (OT) signalling plays a fundamental role in the mechanisms of parturition. OT is one of the most frequently used drugs in obstetrics, promoting uterine contractions for labor induction and augmentation and to prevent postpartum hemorrhage (PPH). Expression of the oxytocin receptor (OTR) in the human myometrium is tightly regulated during pregnancy and its levels have been shown to peak upon labour onset and to fall sharply in advanced labour and the postpartum period, when the uterus become refractive to OT. However, uterine sensitivity to OT varies between pregnant women, probably reflecting differences in their myometrial OTR expression. Control of OTR expression is mediated by a combination of steroid hormone stimulation, stretch, and inflammation. This review summarises current knowledge regarding the complex regulation of myometrial OTR expression and its associated intracellular signaling pathways.
Kassir Y, Sultan L, Malawana J, et al., 2014, PMM.68 Progesterone and cAMP modulate IL1B induced COX2 Inflammation in amnion cells., Arch Dis Child Fetal Neonatal Ed, Vol: 99 Suppl 1
: Preterm labour is the most significant cause of perinatal morbidity and mortality, causing significant socioeconomic consequences for individuals, families and society. Our previous work has demonstrated that cAMP enhances the ability of progesterone to repress IL1B driven COX2 expression in myometrium. The fetal membranes, specifically the amnion, have a potentially significant role in the initiation of labour. Labour being a pro-inflammatory state, potentially could be delayed with the modulation of this inflammatory process. We demonstrated that treatment of primary amnion cell cultures with P4 significantly reduces the IL1B driven COX2 response and that the addition of a cAMP agonist significantly enhances this effect.
Migale R, MacIntyre DA, Lee YS, et al., 2014, TLR4-mediated activation of AP-1 drives the expression of labour associated genes in mouse myometrium, Publisher: WILEY-BLACKWELL, Pages: E10-E10, ISSN: 1470-0328
Nawathe A, Hye KS, Savvidou M, et al., 2014, Insulin-like growth factors and binding protein expressions in fetal growth disorders and maternal diabetes, BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 121, Pages: E2-E3, ISSN: 1470-0328
Chin-Smith EC, Slater DM, Johnson MR, et al., 2014, STIM and oral isoform expression in pregnant human myometrium: a potential role in calcium signaling during pregnancy, Frontiers in Physiology, Vol: 5, ISSN: 1664-042X
Store-operated calcium (Ca2+) entry (SOCE) can be mediated by two novel proteins, STIM/Orai. We have previously demonstrated that members of the TRPC family, putative basal and store operated calcium entry channels, are present in human myometrium and regulated by labor associated stimuli IL-1β and mechanical stretch. Although STIM and Orai isoforms (1-3) have been reported in other smooth muscle cell types, there is little known about the expression or gestational regulation of STIM and Orai expression in human myometrium. Total RNA was isolated from lower segment human myometrial biopsies obtained at Cesarean section from women at the time of preterm no labor (PTNL), preterm labor (PTL), term non-labor (TNL), and term with labor (TL); primary cultured human uterine smooth muscle cells, and a human myometrial cell line (hTERT-HM). STIM1-2, and Orai1-3 mRNA expression was assessed by quantitative real-time PCR. All five genes were expressed in myometrial tissue and cultured cells. STIM1-2 and Orai2-3 expression was significantly lower in cultured cells compared tissue. This has implications with regard investigation of the contribution of these proteins in cultured cells. Orai2 was the most abundant Orai isoform in human myometrium. Expression of STIM1-2/Orai1-3 did not alter with the onset of labor. Orai1 mRNA expression in cultured cells was enhanced by IL-1β treatment. This novel report of STIM1-2 and Orai1-3 mRNA expression in pregnant human myometrium and Orai1 regulation by IL-1β indicates a potential role for these proteins in calcium signaling in human myometrium during pregnancy.
Mitsuya K, Singh N, Sooranna SR, et al., 2014, Epigenetics of Human Myometrium: DNA Methylation of Genes Encoding Contraction-Associated Proteins in Term and Preterm Labor, BIOLOGY OF REPRODUCTION, Vol: 90, ISSN: 0006-3363
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- Citations: 22
MacIntyre DA, Lee YS, Migale R, et al., 2014, Activator protein 1 is a key terminal mediator of inflammation-induced preterm labor in mice, FASEB JOURNAL, Vol: 28, Pages: 2358-2368, ISSN: 0892-6638
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- Citations: 82
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