https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48936 Wed 19 Apr 2023 14:55:13 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:33387 34-weeks gestation; n=8) and gestational age matched preterm (31.6-35.1 weeks; n=8) and term normotensive controls were also compared. Agilent Human miRNA microarray v19 was used to detect up to 2006 miRNAs in four placentae from each group. Statistically different levels of expression were determined and refined using predictive modelling. Placental miRNAs predicted to target RAS mRNAs were identified in three databases. Differences detected on the array were confirmed for some miRNAs by semi-quantitative RT-PCR (qPCR, n=7-8 for all groups). Two differentially expressed miRNAs that were known to target human renal REN mRNA (miR-181a-5p and miR-663) were transfected into human HTR-8/SVneo trophoblast cells to examine their effect on placental REN expression and prorenin levels. In early gestation placentae, 186 miRNAs were differentially expressed compared with term placentae (109 increased, 77 decreased). Thirty of the differentially expressed miRNAs were predicted to target RAS components. In mid-gestation placentae, 117 miRNAs were differentially expressed compared with term placentae (69 increased, 48 decreased). Of these, 19 had RAS mRNAs as predicted targets. Eight miRNAs that were lower in early gestation and predicted to target RAS mRNAs were confirmed by qPCR. All showed an increase during gestation and could influence the transgestational profile of the human placental RAS. Additionally, on the array, three miRNAs predicted to target RAS mRNAs (miR-892c-3p, miR-378c and miR-514b-3p) were overexpressed in placentae from women with late-onset PE (P = 3.6E-10, P = 1.8E-05, P = 5.3E-06; respectively). miR-663, which suppresses renal REN mRNA expression, was overexpressed in early-onset PE placentae as determined by qRT-PCR analysis (P = 0.014). Transfection of miR-181a-5p and miR-663 into HTR-8/SVneo trophoblast cells suppressed REN mRNA expression (p = 0.05) and prorenin protein production (P = 0.001). Data can be found via GEO accession number GSE109832. Further validation that the differentially expressed miRNAs do indeed directly target RAS mRNAs and affect placental development and function is required. This study is limited by the small sample size. Therefore independent validation in a larger cohort is required.]]> Wed 02 Mar 2022 14:28:37 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47669 Tue 24 Jan 2023 15:55:08 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:21455 PR gene and (ii) identified the histone-modifying enzymes that target the H3K4me3 mark at the PR promoters in term and preterm human myometrial tissues obtained before and after labour onset. Bisulphite sequencing showed that despite overall low levels of PR CpG island methylation, there was a significant decrease in methylated CpGs with labour in both preterm (P < 0.05) and term (P < 0.01) groups downstream of the PR-B transcription start site. This methylation change was not associated with altered PR-B expression, but may contribute to the increase in PR-A expression with labour. Chromatin immunoprecipitation revealed that the histone methyltransferase, SET and MYND domain-containing protein 3 (SMYD3), bound to the PR gene at significantly higher levels at the PR-A promoter compared with the PR-B promoter (P < 0.010), with no labour-associated changes observed. The H3K4 demethylase, Jumonji AT-rich interactive domain 1A (JARID1A), also bound to the PR-A, but not to the PR-B promoter prior to term labour, and decreased significantly at the onset of labour (P = 0.014), providing a mechanism for the previously reported increase in H3K4me3 level and PR-A expression with labour. Our studies suggest that epigenetic changes mediated by JARID1A, SMYD3 and DNA methylation may be responsible, at least in part, for the functional progesterone withdrawal that precipitates human labour.]]> Tue 24 Apr 2018 11:46:49 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34014 Thu 30 May 2019 15:41:20 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41699 PTGS2, BMP2 and NAMPT was determined by reverse transcription-coupled quantitative real-Time PCR (qRT-PCR). Chromatin immunoprecipitation (ChIP) and sequential double ChIP were performed to determine the levels and co-occurrence of activating histone-3, lysine-4 trimethylation (H3K4me3) and repressive histone-3, lysine-27 trimethylation (H3K27me3) at the gene promoters. H3K4 methyltransferase, H3K27me3 demethylase and H3K27 methyltransferase expression was determined by qRT-PCR and immunofluorescence confocal microscopy. PTGS2, BMP2 and NAMPT expression was upregulated robustly between early pregnancy and term (P < 0.05). The promoters were marked bivalently by both the H3K4me3 and H3K27me3 modifications. Bivalence was reduced at term by the decrease of the H3K27me3-modified fraction of promoter copies marked by H3K4me3 indicating epigenetic activation. Messenger RNAs encoding the H3K4-specific methyl transferases MLL1,-2,-3,-4, SETD1A,-B and the H3K27me3-specific demethylases KDM6A,-B were expressed increasingly while the H3K27 methyl transferase EZH2 was expressed decreasingly at term. Histone modifying enzyme proteins were detected in amnion epithelial and mesenchymal cells. These results with prototypical proinflammatory genes suggest that nucleosomes at labour-promoting genes are marked bivalently in the amnion, which is shifted towards monovalent H3K4me3 modification at term when the genes are upregulated. Bivalent epigenetic regulation by histone modifying enzymes may control the timing of labour.]]> Thu 11 Aug 2022 14:00:32 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:32118 Thu 03 May 2018 12:11:55 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:13859 Sat 24 Mar 2018 10:39:45 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:9578 Sat 24 Mar 2018 08:34:48 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:17300 Sat 24 Mar 2018 08:01:46 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20323 Sat 24 Mar 2018 07:55:12 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19739 in vitro studies which have refined our understanding of Pi3k/Akt and mTOR signalling in the oocyte and have discovered a role for Jak/Stat/Socs signalling in granulosa cells during primordial follicle activation. We also appraise a novel role for the metal ion zinc in the regulation of meiosis I and meiosis II progression through early meiosis inhibitor (Emi2) and Mos-Mapk signalling, and examine studies which expand our understanding of intracellular calcium signalling and extrinsic Plcζ in stimulating oocyte activation.]]> Sat 24 Mar 2018 07:53:40 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20028 Sat 24 Mar 2018 07:50:55 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:6578 Sat 24 Mar 2018 07:49:15 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:6539 Sat 24 Mar 2018 07:48:19 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:6600 Sat 24 Mar 2018 07:45:36 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:5003 Sat 24 Mar 2018 07:44:13 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:28053 Sat 24 Mar 2018 07:41:03 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27535 Sat 24 Mar 2018 07:28:58 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:28012 Sat 24 Mar 2018 07:27:21 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:4719 Sat 24 Mar 2018 07:21:51 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:24127 Sat 24 Mar 2018 07:16:32 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44774 Mon 24 Oct 2022 09:03:57 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:43861 Mon 20 Feb 2023 11:12:01 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36974 Fri 24 Jul 2020 14:55:41 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19600 ACE A11860G genotype is associated with small for gestational age babies (SGA) and to determine whether the association is affected by environmental factors and fetal sex. Overall, 3234 healthy nulliparous women with singleton pregnancies, their partners and babies were prospectively recruited in Adelaide, Australia and Auckland, New Zealand. Data analyses were confined to 2121 Caucasian parent–infant trios, among which 216 were pregnancies with SGA infants and 1185 were uncomplicated pregnancies. Women with the ACE A11860G GG genotype in the combined and Adelaide cohorts had increased risk for SGA [odds ratios (OR) 1.5, 95% confidence interval (CI) 1.1–2.1 and OR 2.0, 95% CI 1.3–3.3, respectively) and delivered lighter babies (P = 0.02; P = 0.007, respectively) compared with those with AA/AG genotypes. The maternal ACE A11860G GG genotype was associated with higher maternal plasma ACE concentration at 15 weeks' gestation than AA/AG genotypes (P < 0.001). When the Adelaide cohort was stratified by maternal socio-economic index (SEI) and pre-pregnancy green leafy vegetable intake, the ACE A11860G GG genotype was only associated with an increased risk for SGA (OR 4.9, 95% CI 1.8–13.4 and OR 3.3, 95% CI 1.6–7.0, respectively) and a reduction in customized birthweight centile (P = 0.006 and P = 0.03) if superimposed on maternal SEI <34 or pre-pregnancy green leafy vegetable intake <1 serve/day. Furthermore, the associations of maternal ACE A11860G with customized birthweight centile observed among Adelaide women with SEI <34 or pre-pregnancy green leafy vegetable intake <1 serve/day were female specific. The current study identified a novel association of maternal ACE A11860G with SGA. More interestingly, this association was modified by environmental factors and fetal sex, suggesting ACE A11860G–environment–fetal sex interactions.]]> Fri 17 Nov 2023 11:54:01 AEDT ]]>