A case study of the physical, chemical and biological factors affecting dissolved organic carbon in the Warren Reservoir, South Australia / Tanja Jankovic-Karasoulos.

"April 2004"Includes bibliographical references (leaves 308-327)354 leaves : ill. (some col.), maps, plates (col.) ; 30 cm.Thesis (Ph.D.)--University of Adelaide, School of Earth and Environmental Sciences, Discipline of Soil and Land Systems, 200

SCOPE_STOP_Hormones_data_20221214.xlsx

Circulating folate, B12, homocysteine, prolactin (PRL), human placental lactogen (hPL) and placental growth hormone (GH2) were measured in early gestation maternal sera taken from women with uncomplicated pregnancies prior to (SCOPE N=604) and post (STOP N=711) FA food fortification. </p

Haemolysis Detection in MicroRNA-Seq from Clinical Plasma Samples

The abundance of cell-free microRNA (miRNA) has been measured in blood plasma and proposed as a source of novel, minimally invasive biomarkers for several diseases. Despite improvements in quantification methods, there is no consensus regarding how haemolysis affects plasma miRNA content. We propose a method for haemolysis detection in miRNA high-throughput sequencing (HTS) data from libraries prepared using human plasma. To establish a miRNA haemolysis signature we tested differential miRNA abundance between plasma samples with known haemolysis status. Using these miRNAs with statistically significant higher abundance in our haemolysed group, we further refined the set to reveal high-confidence haemolysis association. Given our specific context, i.e., women of reproductive age, we also tested for significant differences between pregnant and non-pregnant groups. We report a novel 20-miRNA signature used to identify the presence of haemolysis in silico in HTS miRNA-sequencing data. Further, we validated the signature set using firstly an all-male cohort (prostate cancer) and secondly a mixed male and female cohort (radiographic knee osteoarthritis). Conclusion: Given the potential for haemolysis contamination, we recommend that assays for haemolysis detection become standard pre-analytical practice and provide here a simple method for haemolysis detection

Characterization of 5-methylcytosine and 5-hydroxymethylcytosine in human placenta cell types across gestation

The placenta is an important organ in pregnancy, however, very little is understood about placental development at a molecular level. This includes the role of epigenetic mechanisms and how they change throughout gestation. DNA methylation studies in this organ are complicated by the different cell types that make up the placenta, each with their own unique transcriptome and epigenome. Placental dysfunction is often associated with pregnancy complications such as preeclampsia (PE). Aberrant DNA methylation in the placenta has been identified in pregnancy complications. We used immunohistochemistry (IHC) and immunofluorescence (IF) to localize 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in placenta tissue from first and second trimester as well as uncomplicated term and PE samples. IHC analysis of whole placental tissues showed 5-mC increased across gestation. When cytotrophoblasts (CTB) and syncytiotrophoblasts (STB) were isolated and assessed using IF, both 5-mC and 5-hmC increased in term CTBs compared to first/second-trimester samples. Staining intensity of 5-hmC was higher in first/second trimester STBs compared to CTBs (P = 0.0011). Finally, IHC staining of term tissue from PE and uncomplicated pregnancies revealed higher 5-mC staining intensity in placentas from PE pregnancies (P = 0.028). Our study has shown increased 5-mC and 5-hmC staining intensities across gestation and differed between two trophoblast populations. Differences in DNA methylation profiles between placental cell types may be indicative of different functions and requires further study to elucidate what changes accompany placental pathologies

Gestational Diabetes Mellitus prevalence and folic acid food fortification: Insights from Australian pregnancy cohorts

Objectives: Gestational diabetes mellitus (GDM) incidence in Australia increased from 5.6% in 2010 to 19.3% in 2022, coinciding with national folic acid (FA) food fortification. High FA intake has been associated with increased insulin resistance and GDM. We examined the association between Australian FA food fortification and maternal folate, placental endocrine function, maternal insulin resistance and GDM incidence.Design and setting: Case control study of two pregnancy cohorts recruited at the same hospital prior to (SCOPE; 2005-2008; Total N=1164) and post (STOP; 2015-2018; Total N=1300) FA food fortification.Outcomes: Circulating folate, red cell folate (RCF), insulin, glucose, prolactin (PRL), human placental lactogen (hPL) and placental growth hormone (GH2) were measured in early pregnancy maternal blood. Results: GDM incidence increased from 5% (SCOPE) to 15.2% (STOP) and was associated with increased maternal folate. Compared to pre-FA fortification, women post-fortification had higher serum folate (18%; pConclusions: GDM is associated with higher maternal folate in early gestation. Excess maternal folate due to FA fortification may alter placental endocrine function to increase insulin resistance and risk of GDM, particularly in women with obesity.Note: Data is in long format with repeated measures for Prolactin, HPL, GH2 and HOMA-IR. Folate, demographics and outcome data only measured at one timepoint.</p

Placental Transcription Profiling in 6&ndash;23 Weeks&rsquo; Gestation Reveals Differential Transcript Usage in Early Development

The human placenta is a rapidly developing transient organ that is key to pregnancy success. Early development of the conceptus occurs in a low oxygen environment before oxygenated maternal blood begins to flow into the placenta at ~10&ndash;12 weeks&rsquo; gestation. This process is likely to substantially affect overall placental gene expression. Transcript variability underlying gene expression has yet to be profiled. In this study, accurate transcript expression profiles were identified for 84 human placental chorionic villus tissue samples collected across 6&ndash;23 weeks&rsquo; gestation. Differential gene expression (DGE), differential transcript expression (DTE) and differential transcript usage (DTU) between 6&ndash;10 weeks&rsquo; and 11&ndash;23 weeks&rsquo; gestation groups were assessed. In total, 229 genes had significant DTE yet no significant DGE. Integration of DGE and DTE analyses found that differential expression patterns of individual transcripts were commonly masked upon aggregation to the gene-level. Of the 611 genes that exhibited DTU, 534 had no significant DGE or DTE. The four most significant DTU genes ADAM10, VMP1, GPR126, and ASAH1, were associated with hypoxia-responsive pathways. Transcript usage is a likely regulatory mechanism in early placentation. Identification of functional roles will facilitate new insight in understanding the origins of pregnancy complications

Antiandrogenic actions of medroxyprogesterone acetate on epithelial cells within normal human breast tissues cultured ex vivo

Objective: Medroxyprogesterone acetate (MPA), a component of combined estrogen-progestin therapy (EPT), has been associated with increased breast cancer risk in EPT users. MPA can bind to the androgen receptor (AR), and AR signaling inhibits cell growth in breast tissues. Therefore, the aim of this study was to investigate the potential of MPA to disrupt AR signaling in an ex vivo culture model of normal human breast tissue. Methods: Histologically normal breast tissues from women undergoing breast surgical operation were cultured in the presence or in the absence of the native AR ligand 5α-dihydrotestosterone (DHT), MPA, or the AR antagonist bicalutamide. Ki67, bromodeoxyuridine, B-cell CLL/lymphoma 2 (BCL2), AR, estrogen receptor α, and progesterone receptor were detected by immunohistochemistry. Results: DHT inhibited the proliferation of breast epithelial cells in an AR-dependent manner within tissues from postmenopausal women, and MPA significantly antagonized this androgenic effect. These hormonal responses were not commonly observed in cultured tissues from premenopausal women. In tissues from postmenopausal women, DHT either induced or repressed BCL2 expression, and the antiandrogenic effect of MPA on BCL2 was variable. MPA significantly opposed the positive effect of DHT on AR stabilization, but these hormones had no significant effect on estrogen receptor α or progesterone receptor levels. Conclusions: In a subset of postmenopausal women, MPA exerts an antiandrogenic effect on breast epithelial cells that is associated with increased proliferation and destabilization of AR protein. This activity may contribute mechanistically to the increased risk of breast cancer in women taking MPA-containing EPT.10 page(s

Maternal Selenium, Copper and Zinc Concentrations in Early Pregnancy, and the Association with Fertility

Trace elements such as zinc, copper, and selenium are essential for reproductive health, but there is limited work examining how circulating trace elements may associate with fertility in humans. The aim of this study was to determine the association between maternal plasma concentrations of zinc, copper, and selenium, and time to pregnancy and subfertility. Australian women (n = 1060) who participated in the multi-centre prospective Screening for Pregnancy Endpoints study were included. Maternal plasma concentrations of copper, zinc and selenium were assessed at 15 &plusmn; 1 weeks&rsquo; gestation. Estimates of retrospectively reported time to pregnancy were documented as number of months to conceive; subfertility was defined as taking more than 12 months to conceive. A range of maternal and paternal adjustments were included. Women who had lower zinc (time ratio, 1.20 (0.99&ndash;1.44)) or who had lower selenium concentrations (1.19 (1.01&ndash;1.40)) had a longer time to pregnancy, equivalent to a median difference in time to pregnancy of around 0.6 months. Women with low selenium concentrations were also at a 1.46 (1.06&ndash;2.03) greater relative risk for subfertility compared to women with higher selenium concentrations. There were no associations between copper and time to pregnancy or subfertility. Lower selenium and zinc trace element concentrations, which likely reflect lower dietary intakes, associate with a longer time to pregnancy. Further research supporting our work is required, which may inform recommendations to increase maternal trace element intake in women planning a pregnancy

Effect of Selenium and Iodine on Oxidative Stress in the First Trimester Human Placenta Explants

Imbalanced maternal micronutrient status, poor placentation, and oxidative stress are associated with greater risk of pregnancy complications, which impact mother and offspring health. As selenium, iodine, and copper are essential micronutrients with key roles in antioxidant systems, this study investigated their potential protective effects on placenta against oxidative stress. First trimester human placenta explants were treated with different concentrations of selenium (sodium selenite), iodine (potassium iodide), their combination or copper (copper (II) sulfate). The concentrations represented deficient, physiological, or super physiological levels. Oxidative stress was induced by menadione or antimycin. Placenta explants were collected, fixed, processed, and embedded for laser ablation inductively coupled plasma-mass spectrometry (LA ICP-MS) element imaging or immunohistochemical labelling. LA ICP-MS showed that placenta could uptake selenium and copper from the media. Sodium selenite and potassium iodide reduced DNA damage and apoptosis (p &lt; 0.05). Following oxidative stress induction, a higher concentration of sodium selenite (1.6 µM) was needed to reduce DNA damage and apoptosis while both concentrations of potassium iodide (0.5 and 1 µM) were protective (p &lt; 0.05). A high concentration of copper (40 µM) increased apoptosis and DNA damage but this effect was no longer significant after induction of oxidative stress. Micronutrients supplementation can increase their content within the placenta and an optimal maternal micronutrient level is essential for placenta health