ORCID Profile
0000-0002-5798-5264
Current Organisations
Griffith University
,
Griffith University Griffith Health
,
Queensland University of Technology
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Publisher: Springer Science and Business Media LLC
Date: 19-11-2018
DOI: 10.1038/S41419-018-1190-9
Abstract: Preecl sia is a devastating pregnancy disorder. Severity varies widely, and while severe preecl sia often requires pre-term delivery, women with mild preecl sia may reach term with minor interventions. The mechanisms that mediate disease severity are poorly understood, but may include adaptive processes by the placenta. We aimed to establish whether in pregnancies that reached term and those that delivered pre-term, the placental response to preecl sia was intrinsically different, and explore potential adaptive mechanisms. Hydrogen peroxide production and antioxidant activity were increased in term preecl tic placentae, whereas pre-term preecl tic placentae had reduced hydrogen peroxide production and reduced function of the antioxidant system superoxide dismutase compared to control placentae. Markers of mitochondrial fission/fusion, apoptosis and the expression level of mitochondrial complexes were differentially disrupted in term compared to pre-term preecl tic placentae. Mitochondrial respiration and content were increased in term preecl tic placentae, but mitochondria had a lower respiratory reserve capacity. Mitochondrial respiration and hydrogen peroxide production were increased in healthy term placentae after in vitro hypoxia/reoxygenation. Placentae from preecl tic pregnancies that reached term showed multiple adaptions that were not present in pre-term preecl tic placentae. Increased antioxidant activity, and expression of markers of mitochondrial fusion and apoptotic suppression, may relate to salvaging damaged mitochondria. Increased mitochondrial respiration may allow ongoing tissue function even with reduced respiratory efficiency in term preecl tic pregnancies. Response after in vitro hypoxia/reoxygenation suggests that disruption of oxygen supply is key to placental mitochondrial adaptations. Reactive oxygen species signalling in term preecl tic placentae may be at a level to trigger compensatory antioxidant and mitochondrial responses, allowing tissue level maintenance of function when there is organelle level dysfunction.
Publisher: Elsevier BV
Date: 03-2013
DOI: 10.1016/J.PLACENTA.2012.11.018
Abstract: Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2012 there were twelve themed workshops, five of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of clinical research and pregnancy disorders: 1) trophoblast deportation 2) gestational trophoblastic disease 3) placental insufficiency and fetal growth restriction 4) trophoblast overinvasion and accreta-related pathologies 5) placental thrombosis and fibrinolysis.
Publisher: CSIRO Publishing
Date: 2017
DOI: 10.1071/RD16382
Abstract: Because reproduction is essential for all life, it is central to our understanding of all aspects of biology. The Society for Reproductive Biology (SRB) 2016 conference held on the Gold Coast (Qld, Australia) displayed the current breadth of reproductive research in Australia and New Zealand, with additional insights from world leaders in the field. This conference review provides a focused summary of the key questions, emerging ideas and novel technologies that were presented in the symposia. Presented research demonstrated key advances in how stem cell biology may allow us to better understand pluripotency, as well as how environmental and lifestyle factors, such as circadian disruption, smoking, alcohol and diet, affect gametogenesis, embryo implantation, placental function and reproductive capacity. Sessions also highlighted the role of reproductive biology in providing insight into the mechanisms and processes governing a wide range of biological science disciplines, including cancer research and therapies, oncofertility, conservation of native species and chronic non-communicable diseases. Recurring themes included the importance of male and female gamete quality for reproductive potential and the critical and varied roles of the placenta in the maintenance of a healthy pregnancy. Dysregulation of reproductive processes can contribute to a variety of pathological states that affect future health, fertility and fecundity. Research being conducted by the SRB has the potential to shape not only the fertility of the current generation, but also the health and reproductive viability of future generations.
Publisher: Elsevier BV
Date: 08-2019
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.PLACENTA.2016.12.022
Abstract: Pregnancy is a physiological challenge that may require additional nutritional support. Suboptimal micronutrient intakes and micronutrient deficiencies during pregnancy are a global problem, often leading to poor maternal and child outcomes. Micronutrient supplementation is commonly recommended during pregnancy to support and enhance maternal metabolism. Recent studies suggest that the use of multiple micronutrient supplements may be of benefit during a normal pregnancy and may significantly reduce the risk of preecl sia, preterm delivery, gestational diabetes, and improve pregnancy outcomes. Given the crucial role that the placenta plays in mediating pregnancy outcomes, it is important to consider the impact of micronutrient supplementation on the mechanisms associated with placental function, as well as maternal and fetal homeostasis. This review will consider the role of key micronutrients in supporting pregnancy and the possible mechanisms by which multiple micronutrients influence placental function and modulate placental oxidative stress and inflammation.
Publisher: Wiley
Date: 04-2020
Publisher: Elsevier BV
Date: 02-2014
DOI: 10.1016/J.PLACENTA.2013.10.014
Abstract: Ask where the maternofetal interface is and placental biologists will tell you, the syncytiotrophoblast and extravillous cytotrophoblasts. While correct, this is not full extent of the maternofetal interface. Trophoblast debris that is extruded into the maternal blood in all pregnancies expands the maternofetal interface to sites remote from the uterus. Trophoblast debris ranges from multinucleated syncytial nuclear aggregates to subcellular micro- and nano-vesicles. The origins of trophoblast debris are not clear. Some propose trophoblast debris is the end of the life-cycle of the trophoblast and that it results from an apoptosis-like cell death, but this is not universally accepted. Knowing whether trophoblast debris results from an apoptosis-like cell death is important because the nature of cell death that produced trophoblast debris will influence the maternal responses to it. Trophoblast debris is challenging to isolate from maternal blood making it difficult to study. However, by culturing placental explants in Netwells™ we can readily harvest trophoblast debris from beneath the Netwells™ which is very similar to debris that has been isolated from pregnant women. We have found that trophoblast debris from normal placentae shows markers of apoptosis and is phagocytosed by macrophages or endothelial cells, producing a tolerant phenotype in the phagocyte. Whereas, when we culture normal placental explants with factors such as antiphospholipid antibodies (a strong maternal risk factor for preecl sia), or IL-6 (which is found at increased levels in the sera of preecl tic women), the death process in the syncytiotrophoblast changes, such that the trophoblast debris becomes more necrotic. Phagocytosis of this necrotic debris leads to activation of endothelial cells. Trophoblast debris greatly expands the maternofetal interface and the nature of that debris is likely to strongly influence the responses of the maternal vascular and immune systems to the debris.
Publisher: Wiley
Date: 15-09-2019
Abstract: Mitochondria are central to cell function. The placenta forms the interface between maternal and fetal systems, and placental mitochondria have critical roles in maintaining pregnancy. The placenta is unusual in having two adjacent cell layers (cytotrophoblasts and the syncytiotrophoblast) with vastly different mitochondria that have distinct functions in health and disease. Mitochondria both produce the majority of reactive oxygen species (ROS), and are sensitive to ROS. ROS are important in allowing cells to sense their environment through mitochondrial-centred signalling, and this signalling also helps cells/tissues adapt to changing environments. However, excessive ROS are damaging, and increased ROS levels are associated with pregnancy complications, including the important disorders preecl sia and gestational diabetes mellitus. Here we review the function of placental mitochondria in healthy pregnancy, and also in pregnancy complications. Placental mitochondria are critical to cell function, and mitochondrial damage is a feature of pregnancy complications. However, the responsiveness of mitochondria to ROS signalling may be central to placental adaptations that mitigate damage, and placental mitochondria are an attractive target for the development of therapeutics to improve pregnancy outcomes.
Publisher: Elsevier BV
Date: 09-2016
Publisher: Hindawi Limited
Date: 03-12-2019
DOI: 10.1155/2019/5764740
Abstract: Scope . Milk provides a natural means of nutrient supply to infants. Exosomes are an important component of milk that are not only being studied for their promise in translational medicine but also in infant nutrition. They also play important roles in intercellular communication and immune function in mammary glands and are able to transfer their materials to the recipient. Therefore, the isolation of high-quality exosomes is an important aspect of exosome research. Methods and Results . This study is a technical study, which provides a detailed methodology for the isolation and enrichment of exosomes from milk. In this study, we evaluate the suitability of using the exosome enrichment method that we have recently published for bovine milk, on human milk. We initially isolated extracellular vesicles from human and bovine milk on a fresh set of s les, using ultracentrifugation, and then exosomes were subsequently enriched via size exclusion chromatography (SEC). Following isolation and enrichment, exosomes from both species were characterized by particle concentration (nanoparticle tracking analysis, NTA), morphology (transmission electron microscopy, TEM), and the presence of exosomal markers (immunoblotting and mass spectrometry using information dependant acquisition (IDA)). The key exosomal characteristics of spherical/donut-shaped morphology, the presence of exosomal markers, e.g., FLOT-1 and the tetraspanins, CD9 and CD81), and particle concentration were confirmed in both human and bovine milk exosomes. Conclusion . We conclude that our robust exosome enrichment method, previously published for bovine milk, is suitable for use on human milk.
Publisher: MDPI AG
Date: 26-10-2020
DOI: 10.3390/IJMS21217941
Abstract: Mitochondria are essential cellular organelles, controlling multiple signalling pathways critical for cell survival and cell death. Increasing evidence suggests that mitochondrial metabolism and functions are indispensable in tumorigenesis and cancer progression, rendering mitochondria and mitochondrial functions as plausible targets for anti-cancer therapeutics. In this review, we summarised the major strategies of selective targeting of mitochondria and their functions to combat cancer, including targeting mitochondrial metabolism, the electron transport chain and tricarboxylic acid cycle, mitochondrial redox signalling pathways, and ROS homeostasis. We highlight that delivering anti-cancer drugs into mitochondria exhibits enormous potential for future cancer therapeutic strategies, with a great advantage of potentially overcoming drug resistance. Mitocans, exemplified by mitochondrially targeted vitamin E succinate and tamoxifen (MitoTam), selectively target cancer cell mitochondria and efficiently kill multiple types of cancer cells by disrupting mitochondrial function, with MitoTam currently undergoing a clinical trial.
Publisher: BMJ
Date: 11-03-2022
DOI: 10.1136/BJSPORTS-2021-104795
Abstract: To review risk factors associated with acute respiratory illness (ARill) in athletes, including non-infectious ARill and suspected or confirmed acute respiratory infections (ARinf). Systematic review. Electronic databases: PubMed-Medline, EbscoHost and Web of Science. Original research articles published between January 1990 and July 2020 in English were searched for prospective and retrospective full text studies that reported quantitative data on risk factors associated with ARill/ARinf in athletes, at any level of performance (elite/non-elite), aged 15–65 years. 48 studies (n=19 390 athletes) were included in the study. Risk factors associated with ARill/ARinf were: increased training monotony, endurance training programmes, lack of tapering, training during winter or at altitude, international travel and vitamin D deficits. Low tear-(SIgA) and salivary-(IgA) were immune biomarkers associated with ARill/ARinf. Modifiable training and environmental risk factors could be considered by sports coaches and athletes to reduce the risk of ARill/ARinf. Clinicians working with athletes can consider assessing and treating specific nutritional deficiencies such as vitamin D. More research regarding the role and clinical application of measuring immune biomarkers in athletes at high risk of ARill/ARinf is warranted. CRD42020160928.
Publisher: Cell Physiol Biochem Press GmbH and Co KG
Date: 18-02-2019
DOI: 10.33594/000000007
Publisher: Springer Science and Business Media LLC
Date: 12-06-2008
DOI: 10.1007/S00251-008-0300-8
Abstract: We have investigated the ersity of class II major histocompatibility complex (MHC) loci in the brushtail possum (Trichosurus vulpecula), an important marsupial pest species in New Zealand. Immunocontraceptive vaccines, a method of fertility control that employs the immune system to attack reproductive cells or proteins, are currently being researched as a means of population control for the possum. Variation has been observed in the immune response of in idual possums to immunocontraceptives. If this variability is under genetic control, it could compromise vaccine efficacy through preferential selection of animals that fail to mount a significant immune response and remain fertile. The MHC is an important immune region for antigen presentation and as such may influence the response to immunocontraceptives. We used known marsupial MHC sequences to design polymerase chain reaction primers to screen for possum MHC loci. Alpha and beta chains from two class II families, DA and DB, were found in possums throughout New Zealand. Forty new class II MHC alleles were identified in the possum, and the levels of variability in the MHC of this marsupial appear to be comparable to those of eutherian species. Preliminary population surveys showed evidence of clustering/variability in the distribution of MHC alleles in geographically separate locations. The extensive variation demonstrated in possums reinforces the need for further research to assess the risk that such MHC variation poses for long-term immunocontraceptive vaccine efficacy.
Publisher: Wiley
Date: 20-05-2019
DOI: 10.1113/JP277815
Publisher: MDPI AG
Date: 14-03-2021
DOI: 10.3390/IJMS22062946
Abstract: Linoleic acid (LA), an n-6 polyunsaturated fatty acid (PUFA), is essential for fetal growth and development. We aimed to investigate the effect of maternal and postnatal high LA (HLA) diet on plasma FA composition, plasma and hepatic lipids and genes involved in lipid metabolism in the liver of adult offspring. Female rats were fed with low LA (LLA 1.44% LA) or HLA (6.21% LA) diets for 10 weeks before pregnancy, and during gestation/lactation. Offspring were weaned at postnatal day 25 (PN25), fed either LLA or HLA diets and sacrificed at PN180. Postnatal HLA diet decreased circulating total n-3 PUFA and alpha-linolenic acid (ALA), while increased total n-6 PUFA, LA and arachidonic acid (AA) in both male and female offspring. Maternal HLA diet increased circulating leptin in female offspring, but not in males. Maternal HLA diet decreased circulating adiponectin in males. Postnatal HLA diet significantly decreased aspartate transaminase (AST) in females and downregulated total cholesterol, HDL-cholesterol and triglycerides in the plasma of males. Maternal HLA diet downregulated the hepatic mRNA expression of Hmgcr in both male and female offspring and decreased the hepatic mRNA expression of Cpt1a and Acox1 in females. Both maternal and postnatal HLA diet decreased hepatic mRNA expression of Cyp27a1 in females. Postnatal diet significantly altered circulating fatty acid concentrations, with sex-specific differences in genes that control lipid metabolism in the adult offspring following exposure to high LA diet in utero.
Publisher: Frontiers Media SA
Date: 23-12-2020
DOI: 10.3389/FPHYS.2020.594313
Abstract: The roles that eicosanoids play during pregnancy and parturition are crucial to a successful outcome. A better understanding of the regulation of eicosanoid production and the roles played by the various end products during pregnancy and parturition has led to our view that accurate measurements of a panel of those end products has exciting potential as diagnostics and prognostics of preterm labor and delivery. Exosomes and their contents represent an exciting new area for research of movement of key biological factors circulating between tissues and organs akin to a parallel endocrine system but involving key intracellular mediators. Eicosanoids and enzymes regulating their biosynthesis and metabolism as well as regulatory microRNAs have been identified within exosomes. In this review, the regulation of eicosanoid production, abundance and actions during pregnancy will be explored. Additionally, the functional significance of placental exosomes will be discussed.
Publisher: Elsevier BV
Date: 2012
Publisher: Elsevier BV
Date: 02-2012
Publisher: Elsevier BV
Date: 09-2017
Publisher: Wiley
Date: 04-2020
Publisher: Wiley
Date: 28-01-2020
Abstract: Maternal nutrition plays a critical role in fetal development and can influence adult onset of disease. Linoleic acid (LA) and alpha‐linolenic acid (ALA) are major omega‐6 (n‐6) and n‐3 polyunsaturated fatty acids (PUFA), respectively, that are essential in our diet. LA and ALA are critical for the development of the fetal neurological and immune systems. However, in recent years, the consumption of n‐6 PUFA has increased gradually worldwide, and elevated n‐6 PUFA consumption may be harmful to human health. Consumption of diets with high levels of n‐6 PUFA before or during pregnancy may have detrimental effects on fetal development and may influence overall health of offspring in adulthood. This review discusses the role of n‐6 PUFA in fetal programming, the importance of a balance between n‐6 and n‐3 PUFAs in the maternal diet, and the need of further animal models and human studies that critically evaluate both n‐6 and n‐3 PUFA contents in diets.
Publisher: Cambridge University Press (CUP)
Date: 16-04-2022
DOI: 10.1017/S0007114521001276
Abstract: Linoleic acid (LA), an essential n -6 fatty acid (FA), is critical for fetal development. We investigated the effects of maternal high LA (HLA) diet on offspring cardiac development and its relationship to circulating FA and cardiovascular function in adolescent offspring, and the ability of the postnatal diet to reverse any adverse effects. Female Wistar Kyoto rats were fed low LA (LLA 1·44 % energy from LA) or high LA (HLA 6·21 % energy from LA) diets for 10 weeks before pregnancy and during gestation/lactation. Offspring, weaned at postnatal day 25, were fed LLA or HLA diets and euthanised at postnatal day 40 ( n 6–8). Maternal HLA diet decreased circulating total cholesterol and HDL-cholesterol in females and decreased total plasma n -3 FA in males, while maternal and postnatal HLA diets decreased total plasma n -3 FA in females. α -Linolenic acid (ALA) and EPA were decreased by postnatal but not maternal HLA diets in both sexes. Maternal and postnatal HLA diets increased total plasma n -6 and LA, and a maternal HLA diet increased circulating leptin, in both male and female offspring. Maternal HLA decreased slopes of systolic and diastolic pressure–volume relationship (PVR), and increased cardiac Col1a1 , Col3a1 , Atp2a1 and Notch1 in males. Maternal and postnatal HLA diets left-shifted the diastolic PVR in female offspring. Coronary reactivity was altered in females, with differential effects on flow repayment after occlusion. Thus, maternal HLA diets impact lipids, FA and cardiac function in offspring, with postnatal diet modifying FA and cardiac function in the female offspring.
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.PLACENTA.2015.11.014
Abstract: Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2015 there were twelve themed workshops, three of which are summarized in this report. These workshops covered areas of placental regulation and nutrient handling: 1) placental epigenetics 2) placental mitochondrial function 3) placental transport systems.
Publisher: Elsevier BV
Date: 10-2009
DOI: 10.1016/J.JRI.2009.04.008
Abstract: The possum is a major invasive pest in New Zealand. One option for its control is the use of immunocontraceptive vaccines. Initial trials of vaccines have shown in idual variation in response. The use of vaccines on wild populations could result in the evolution of a resistant population through selection for possums that remain fertile because of low or no response. Understanding the basis of this variation is therefore important. The major histocompatibility complex (MHC) is an important influence on the nature of immune responses. This study has investigated the relationship between MHC alleles and in idual immune responses to immunocontraceptive vaccines comprising zona pellucida peptides. We identified MHC alleles and putative haplotypes, and compared these between in iduals with measured responses to immunocontraceptive vaccines. Two haplotypes were found to associate significantly with differences in vaccine response. Possums that carried haplotype 6 showed reduced responsiveness to one vaccine, while possums that carried haplotype 9 showed increased responsiveness to a separate vaccine. The identification of MHC haplotypes associated with different responses to immunocontraceptive vaccines offers the opportunity to understand what factors trigger non-response and the persistence of fertility in some in iduals, and may allow vaccines to be optimised to minimise non-responsiveness.
Publisher: Elsevier
Date: 2020
Publisher: Wiley
Date: 13-03-2018
DOI: 10.1111/IWJ.12907
Publisher: Elsevier BV
Date: 09-2015
Publisher: MDPI AG
Date: 23-09-2021
Abstract: Background: Linoleic acid (LA) is an essential polyunsaturated fatty acid (PUFA) that is required for foetal growth and development. Excess intake of LA can be detrimental for metabolic health due to its pro-inflammatory properties however, the effect of a diet high in LA on offspring metabolites is unknown. In this study, we aimed to determine the role of maternal or postnatal high linoleic acid (HLA) diet on plasma metabolites in adult offspring. Methods: Female Wistar Kyoto (WKY) rats were fed with either low LA (LLA) or HLA diet for 10 weeks prior to conception and during gestation/lactation. Offspring were weaned at postnatal day 25 (PN25), treated with either LLA or HLA diets and sacrificed at PN180. Metabolite analysis was performed in plasma s les using Nuclear Magnetic Resonance. Results: Maternal and postnatal HLA diet did not alter plasma metabolites in male and female adult offspring. There was no specific clustering among different treatment groups as demonstrated by principal component analysis. Interestingly, there was clustering among male and female offspring independent of maternal and postnatal dietary intervention. Lysine was higher in female offspring, while 3-hydroxybutyric acid and acetic acid were significantly higher in male offspring. Conclusion: In summary, maternal or postnatal HLA diet did not alter the plasma metabolites in the adult rat offspring however, differences in metabolites between male and female offspring occurred independently of dietary intervention.
Publisher: Springer Science and Business Media LLC
Date: 05-11-2016
DOI: 10.1007/S12011-016-0870-5
Abstract: The human placenta provides life support for the developing foetus, and a healthy placenta is a prerequisite to a healthy start to life. Placental tissue is subject to oxidative stress which can lead to pathological conditions of pregnancy such as preecl sia, preterm labour and intrauterine growth restriction. Up-regulation of endogenous anti-oxidants may alleviate placental oxidative stress and provide a therapy for these complications of pregnancy. In this study, selenium supplementation, as inorganic sodium selenite (NaSel) or organic selenomethionine (SeMet), was used to increase the protein production and cellular activity of the important redox active proteins glutathione peroxidase (GPx) and thioredoxin reductase (Thx-Red). Placental trophoblast cell lines, BeWo, JEG-3 and Swan-71, were cultured in various concentrations of NaSel or SeMet for 24 h and cell extracts prepared for western blots and enzyme assays. Rotenone and antimycin were used to stimulate mitochondrial reactive oxygen species (ROS) production and induce apoptosis. Trophoblast cells supplemented with 100 nM NaSel and 500 nM SeMet exhibited significantly enhanced expression and activity of both GPx and Thx-Red. Antimycin and rotenone were found to generate ROS when measured by 2',7'-dichlorofluorescein diacetate (DCFDA) assay, and selenium supplementation was shown to reduce ROS production in a dose-dependent manner. Rotenone, 100 μM treatment for 4 h, caused trophoblast cell apoptosis as evidenced by increased Annexin V binding and decreased expression of Bcl-2. In both assays of apoptosis, selenium supplementation was able to prevent apoptosis, preserve Bcl-2 expression and protect trophoblast cells from mitochondrial oxidative stress. This data suggests that selenoproteins such as GPx and Thx-Red have an important role in protecting trophoblast cells from mitochondrial oxidative stress and that selenium supplementation may be important in treating some placental pathologies.
Publisher: Springer Science and Business Media LLC
Date: 25-08-2005
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.PLACENTA.2015.06.010
Abstract: Placental oxidative stress has been implicated in pregnancy complications and previous work has shown that selenium can protect trophoblast mitochondria from oxidative stress. This report examines mitochondrial function and content in trophoblasts supplemented with selenium. Swan-71, JEG-3 and BeWo cells and placental tissue were incubated with sodium selenite or selenomethionine. Mitochondrial function was examined in a respirometer. Mitochondrial content was determined using RT-PCR. The levels of the mitochondrial biogenesis markers selenoprotein H, PGC-1α and NRF-1 was examined by western blotting. Mitochondrial respiration was significantly enhanced post selenium supplementation in cells and tissues. Selenium supplementation increased mitochondrial content and up-regulated mitochondrial biogenesis mediators in cells. These results emphasise the importance of selenium in mitochondrial regeneration in trophoblasts.
Publisher: Elsevier BV
Date: 08-2019
Publisher: Wiley
Date: 06-03-2015
DOI: 10.1111/MEC.13102
Abstract: Invasive, non-native species are one of the major causes of global bio ersity loss. Although they are, by definition, successful in their non-native range, their populations generally show major reductions in their genetic ersity during the demographic bottleneck they experience during colonization. By investigating the mitochondrial genetic ersity of an invasive non-native species, the stoat Mustela erminea, in New Zealand and comparing it to ersity in the species' native range in Great Britain, we reveal the opposite effect. We demonstrate that the New Zealand stoat population contains four mitochondrial haplotypes that have not been found in the native range. Stoats in Britain rely heavily on introduced rabbits Oryctolagus cuniculus as their primary prey and were introduced to New Zealand in a misguided attempt at biological control of rabbits, which had also been introduced there. While invasive stoats have since decimated the New Zealand avifauna, native stoat populations were themselves decimated by the introduction to Britain of Myxoma virus as a control measure for rabbits. We highlight the irony that while introduced species (rabbits) and subsequent biocontrol (myxomatosis) have caused population crashes of native stoats, invasive stoats in New Zealand, which were also introduced for biological control, now contain more genetic haplotypes than their most likely native source.
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.PLACENTA.2017.06.011
Abstract: Placental mitochondria are subjected to micro-environmental changes throughout gestation, in particular large variations in oxygen. How placental mitochondrial respiration adapts to changing oxygen concentrations remains unexplored. Additionally, placental tissue is often studied in culture however, the effect of culture on placental mitochondria is unclear. Placental tissue was obtained from first trimester and term (laboured and non-laboured) pregnancies, and selectively permeabilized to access mitochondria. Respirometry was used to compare respiration states and substrate use in mitochondria. Additionally, explants of placental tissue were cultured for four, 12, 24, 48, or 96 h and respiration measured. Mitochondrial respiration decreased at 11 weeks compared to earlier gestations (p = 0.05-0.001), and mitochondrial content increased at 12-13 weeks compared to 7-10 weeks (p = 0.042). In term placentae, oxidative phosphorylation (OXPHOS) through mitochondrial complex IV (p < 0.001), the relative proportion of OXPHOS CI (p < 0.001), the total capacity of the respiratory system (p = 0.003), and mitochondrial content (p < 0.001) were higher compared to first trimester. Respiration was increased (p ≤ 0.006-0.001) in laboured compared to non-laboured placenta. After four hours of culture, respiration was depressed compared to fresh tissue from the same placenta and continued to decline with time in culture. Markers of apoptosis were increased, while markers of autophagy, mitochondrial biogenesis, and mitochondrial membrane potential were decreased after four hours of culture. Respiration and mitochondrial content alter over gestation/with labour. Decreased respiration at 11 weeks and increased mitochondrial content at 12-13 weeks may relate to onset of maternal blood flow, and increased respiration as a result of labour may be an adaptation to ischaemia-reperfusion. At term, mitochondria were more susceptible to changes in respiratory function relative to first trimester when cultured in vitro, perhaps reflecting changes in metabolic demands as gestation progresses. Metabolic plasticity of placental mitochondria has relevance to placenta-mediated diseases.
Publisher: Springer Science and Business Media LLC
Date: 29-08-2008
DOI: 10.1007/S00251-008-0327-X
Abstract: The ersity of class II major histocompatibility complex (MHC) loci was investigated in the brushtail possum, an important marsupial pest species in New Zealand. Immunocontraception, a form of fertility control that generates an autoimmune response, is being developed as a population control method for the possum. Because the immune response is partly under genetic control, an understanding of immunogenetics in possum will be crucial to the development of immunocontraceptive vaccines. MHC molecules are critical in the vertebrate immune response. Class II MHC molecules bind and present exogenously derived peptides to T lymphocytes and may be important in the presentation of immunocontraceptives. We used polymerase chain reaction primers designed to lify the peptide binding region of possum class II MHC genes to isolate sequences from 49 animals. We have previously described 19 novel alleles from the DAB locus in the possum (Holland et al., Immunogenetics 60:449-460, 2008). Here, we report on another 11 novel alleles isolated from possum DAB, making this the most erse marsupial locus described so far. This high level of ersity indicates that DAB is an important MHC locus in the possum and will need to be taken into account in the design of immunocontraceptive vaccines.
Publisher: Elsevier BV
Date: 09-2017
Publisher: Informa UK Limited
Date: 28-05-2014
DOI: 10.3109/14647273.2014.907506
Abstract: SPRASA (also referred to as SLLP1) is a protein identified in the acrosome of human sperm and encoded by the gene SPACA3. SPRASA is associated with sperm-oocyte recognition and binding, and may play a role in fertility. In order to determine whether variants in the SPACA3 gene are associated with human infertility, we undertook a genetic analysis of 102 infertile and 104 fertile couples. Three gene variants were identified using PCR-based DNA sequencing 1) an insertion of TGC within a quadruple tri-nucleotide (TGC) repeat region in the 5' untranslated region (UTR) (g.-22TGC(4_5), 2) a guanine to adenosine transition at position 239 (c.239G>A) resulting in a non-synonymous amino acid substitution from cysteine to tyrosine (p.C80Y) at position 80 in the putative transmembrane region, and 3) a novel nucleotide variant (c.691G>C) located in the 3'UTR. A functional effect of the g.-22TGC (4_5) was confirmed by a luciferase expression assay, while the effects of the variants c.239G>A and c.691G>C were predicted using in silico analysis. Although the frequencies of these variants were not significantly different between the infertile and fertile populations, we present evidence that the variants could affect the expression levels or function of SPRASA, thereby affecting a couple's fertility. Larger populations, especially in iduals/couples with unexplained infertility, need to be screened for these variants to validate a relationship with fertility.
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.PLACENTA.2017.01.119
Abstract: Pregnancy is one of the greatest physiological challenges that a women can experience. The physiological adaptations that accompany pregnancy may increase the risk of developing a number of disorders that can lead to both acute and chronic physiological outcomes. In addition, fetal development may be impaired and, if the fetus survives, the child may be at an increased risk of disease throughout life. Pregnancy disorders are poorly predicted by traditional risk factors and maternal history alone. The identification of biomarkers that can predict incidence and severity of disease would allow for improved and targeted prophylactic therapies to prevent adverse maternal and fetal outcomes. Many of these pregnancy disorders, including preecl sia, intrauterine growth restriction, gestational diabetes mellitus and preterm birth are known to be regulated at least in part by poor trophoblast invasion and/or dysregulated placental function. Cellular stress within the placenta increases the release of a number of factors into the maternal circulation. While many of these factors minimally impact maternal biology, others affect key physiological systems and contribute to disease. Importantly, these factors may be detected in physiological fluids and have predictive capacity making them ideal candidates as biomarkers of pregnancy disorders. This review will discuss what is known about these placental derived biomarkers of pregnancy disorders and highlight potential clinical opportunities for disease prediction and diagnosis.
Publisher: Wiley
Date: 05-2021
Publisher: MDPI AG
Date: 02-12-2019
DOI: 10.3390/IJMS20236079
Abstract: Epilepsy is a neurological disorder that affects approximately 50 million people worldwide. There is currently no definitive epilepsy cure. However, in recent years, medicinal cannabis has been successfully trialed as an effective treatment for managing epileptic symptoms, but whose mechanisms of action are largely unknown. Lately, there has been a focus on neuroinflammation as an important factor in the pathology of many epileptic disorders. In this literature review, we consider the links that have been identified between epilepsy, neuroinflammation, the endocannabinoid system (ECS), and how cannabinoids may be potent alternatives to more conventional pharmacological therapies. We review the research that demonstrates how the ECS can contribute to neuroinflammation, and could therefore be modulated by cannabinoids to potentially reduce the incidence and severity of seizures. In particular, the cannabinoid cannabidiol has been reported to have anti-convulsant and anti-inflammatory properties, and it shows promise for epilepsy treatment. There are a multitude of signaling pathways that involve endocannabinoids, eicosanoids, and associated receptors by which cannabinoids could potentially exert their therapeutic effects. Further research is needed to better characterize these pathways, and consequently improve the application and regulation of medicinal cannabis.
Publisher: BMJ
Date: 08-03-2022
DOI: 10.1136/BJSPORTS-2021-104737
Abstract: To determine the incidence of acute respiratory illness (ARill) in athletes and by method of diagnosis, anatomical classification, ages, levels of performance and seasons. Systematic review and meta-analysis. Electronic databases: PubMed-Medline, EbscoHost and Web of Science. Original research articles published between January 1990 and July 2020 in English reporting the incidence of ARill in athletes, at any level of performance (elite/non-elite), aged 15–65 years. Across all 124 studies (n=1 28 360 athletes), the incidence of ARill, estimated by iding the number of cases by the total number of athlete days, was 4.7 (95% CI 3.9 to 5.7) per 1000 athlete days. In studies reporting acute respiratory infections (ARinf suspected and confirmed) the incidence was 4.9 (95% CI 4.0 to 6.0), which was similar in studies reporting undiagnosed ARill (3.7 95% CI 2.1 to 6.7). Incidences of 5.9 (95% CI 4.8 to 7.2) and 2.8 (95% CI 1.8 to 4.5) were found for studies reporting upper ARinf and general ARinf (upper or lower), respectively. The incidence of ARinf was similar across the different methods to diagnose ARinf. A higher incidence of ARinf was found in non-elite (8.7 95% CI 6.1 to 12.5) vs elite athletes (4.2 95% CI 3.3 to 5.3). These findings suggest: (1) the incidence of ARill equates to approximately 4.7 per athlete per year (2) the incidence of upper ARinf was significantly higher than general (upper/lower) ARinf (3) elite athletes have a lower incidence of ARinf than non-elite athletes (4) if pathogen identification is not available, physicians can confidently use validated questionnaires and checklists to screen athletes for suspected ARinf. For future studies, we recommend that a clear diagnosis of ARill is reported. CRD42020160472.
Publisher: Springer Science and Business Media LLC
Date: 04-2015
Publisher: Frontiers Media SA
Date: 08-03-2021
DOI: 10.3389/FPHAR.2021.586715
Abstract: Background: Circulating bilirubin is associated with reduced adiposity in human and animal studies. A possible explanation is provided by in vitro data that demonstrates that bilirubin inhibits mitochondrial function and decreases efficient energy production. However, it remains unclear whether hyperbilirubinemic animals have similar perturbed mitochondrial function and whether this is important for regulation of energy homeostasis. Aim: To investigate the impact of unconjugated hyperbilirubinemia on body composition, and mitochondrial function in hepatic tissue and skeletal muscle. Materials and Methods: 1) Food intake and bodyweight gain of 14-week old hyperbilirubinemic Gunn ( n = 19) and normobilirubinemic littermate (control n = 19) rats were measured over a 17-day period. 2) Body composition was determined using dual-energy X-ray absorptiometry and by measuring organ and skeletal muscle masses. 3) Mitochondrial function was assessed using high-resolution respirometry of homogenized liver and intact permeabilized extensor digitorum longus and soleus fibers. 4) Liver tissue was flash frozen for later gene (qPCR), protein (Western Blot and citrate synthase activity) and lipid analysis. Results: Female hyperbilirubinemic rats had significantly reduced fat mass (Gunn: 9.94 ± 5.35 vs. Control: 16.6 ± 6.90 g, p & 0.05) and hepatic triglyceride concentration (Gunn: 2.39 ± 0.92 vs. Control: 4.65 ± 1.67 mg g −1 , p & 0.01) compared to normobilirubinemic controls. Furthermore, hyperbilirubinemic rats consumed fewer calories daily ( p & 0.01) and were less energetically efficient (Gunn: 8.09 ± 5.75 vs. Control: 14.9 ± 5.10 g bodyweight kcal −1 , p & 0.05). Hepatic mitochondria of hyperbilirubinemic rats demonstrated increased flux control ratio (FCR) via complex I and II (CI+II) (Gunn: 0.78 ± 0.16 vs. Control: 0.62 ± 0.09, p & 0.05). Similarly, exogenous addition of 31.3 or 62.5 μM unconjugated bilirubin to control liver homogenates significantly increased CI+II FCR ( p & 0.05). Hepatic PGC-1α gene expression was significantly increased in hyperbilirubinemic females while FGF21 and ACOX1 was significantly greater in male hyperbilirubinemic rats ( p & 0.05). Finally, hepatic mitochondrial complex IV subunit 1 protein expression was significantly increased in female hyperbilirubinemic rats ( p & 0.01). Conclusions: This is the first study to comprehensively assess body composition, fat metabolism, and mitochondrial function in hyperbilirubinemic rats. Our findings show that hyperbilirubinemia is associated with reduced fat mass, and increased hepatic mitochondrial biogenesis, specifically in female animals, suggesting a dual role of elevated bilirubin and reduced UGT1A1 function on adiposity and body composition.
Publisher: Elsevier BV
Date: 09-2017
Publisher: AIP Publishing
Date: 30-03-2020
DOI: 10.1063/1.5144977
Abstract: The scaling relations for the dispersion coefficients of long-range interactions between the Mu(1s)–Mu(1s, 2s, or 2p) systems and the H(1s)–H(1s, 2s, or 2p) systems are obtained using analytical properties of hydrogenic wavefunctions, which allows us to obtain the dispersion coefficients for Mu(1s)–Mu(1s, 2s, or 2p) systems from the corresponding H(1s)–H(1s, 2s, or 2p) systems. Additionally, the dispersion coefficients of long-range interactions of Mu(1s) with the ground-state H, noble gas atoms He, Ne, Ar, Kr, and Xe, alkali-metal atoms Li, Na, K, and Rb, alkaline-earth atoms Be, Mg, Ca, and Sr, and Cu, Ag, F, and Cl atoms are calculated.
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.PLACENTA.2016.12.012
Abstract: The aetiology of many gestational disorders is still unknown. However, insufficient trans-placental nutrient and oxygen transfer due to abnormal placentation is characteristic of several pathologies, and may alter the function of placental mitochondria. Mitochondria are multifunctional organelles that respond to a wide range of stimuli - such as physiological changes in cellular energy demands or various pathologies - by reshaping via fusion or fission, increasing/decreasing in number, altering oxidative phosphorylation, and signalling cellular functions such as apoptosis. Mitochondrial function is integral to tissue functions including energy production, metabolism, and regulation of various cellular responses including response to oxidative stress. This review details the functions of placental mitochondria and investigates mitochondrial function and structure in gestational disorders including preecl sia, intrauterine growth restriction, diabetes mellitus, and obesity. Placental mitochondrial dysfunction may be critical in a range of gestational disorders which have important implications for maternal and fetal/offspring health.
Publisher: Frontiers Media SA
Date: 03-2023
DOI: 10.3389/FPHYS.2023.1143543
Abstract: Preecl sia is a progressive, multisystem pregnancy disorder. According to the time of onset or delivery, preecl sia has been subclassified into early-onset (& weeks) and late-onset (≥34 weeks), or preterm (& weeks) and term (≥37 weeks). Preterm preecl sia can be effectively predicted at 11–13 weeks well before onset, and its incidence can be reduced by preventively using low-dose aspirin. However, late-onset and term preecl sia are more prevalent than early forms and still lack effective predictive and preventive measures. This scoping review aims to systematically identify the evidence of predictive biomarkers reported in late-onset and term preecl sia. This study was conducted based on the guidance of the Joanna Briggs Institute (JBI) methodology for scoping reviews. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for scoping reviews (PRISMA-ScR) was used to guide the study. The following databases were searched for related studies: PubMed, Web of Science, Scopus, and ProQuest. Search terms contain “preecl sia,” “late-onset,” “term,” “biomarker,” or “marker,” and other synonyms combined as appropriate using the Boolean operators “AND” and “OR.” The search was restricted to articles published in English from 2012 to August 2022. Publications were selected if study participants were pregnant women and biomarkers were detected in maternal blood or urine s les before late-onset or term preecl sia diagnosis. The search retrieved 4,257 records, of which 125 studies were included in the final assessment. The results demonstrate that no single molecular biomarker presents sufficient clinical sensitivity and specificity for screening late-onset and term preecl sia. Multivariable models combining maternal risk factors with biochemical and/or biophysical markers generate higher detection rates, but they need more effective biomarkers and validation data for clinical utility. This review proposes that further research into novel biomarkers for late-onset and term preecl sia is warranted and important to find strategies to predict this complication. Other critical factors to help identify candidate markers should be considered, such as a consensus on defining preecl sia subtypes, optimal testing time, and s le types.
Publisher: Elsevier BV
Date: 03-2020
Publisher: American Physiological Society
Date: 02-2020
DOI: 10.1152/AJPENDO.00265.2019
Abstract: Dietary intakes of linoleic acid (LA) have increased, including in women of reproductive age. Changes in maternal gut microbiome have been implicated in the metabolic adaptions that occur during pregnancy. We aimed to investigate whether consumption of a diet with elevated LA altered fecal microbiome ersity before and during pregnancy. Female Wistar-Kyoto rats consumed a high-LA diet (HLA: 6.21% of energy) or a low-LA diet (LLA: 1.44% of energy) for 10 wk before mating and during pregnancy. DNA was isolated from fecal s les before pregnancy [embryonic day 0 (E0)], or during pregnancy at E10 and E20. The microbiome composition was assessed with 16S rRNA sequencing. At E0, the beta- ersity of LLA and HLA groups differed with HLA rats having significantly lower abundance of the genera Akkermansia, Peptococcus, Sutterella, and Xo2d06 but higher abundance of Butyricimonas and Coprococcus. Over gestation, in LLA but not HLA rats, there was a reduction in alpha- ersity and an increase in beta- ersity. In the LLA group, the abundance of Akkermansia, Blautia, rc4.4, and Streptococcus decreased over gestation, whereas Coprococcus increased. In the HLA group only the abundance of Butyricimonas decreased. At E20, there were no differences in alpha- and beta- ersity, and the abundance of Roseburia was significantly increased in the HLA group. In conclusion, consumption of a HLA diet alters gut microbiota composition, as does pregnancy in rats consuming a LLA diet. In pregnancy, consumption of a HLA diet does not alter gut microbiota composition.
Publisher: MDPI AG
Date: 23-07-2020
DOI: 10.3390/NU12082183
Abstract: Fetal development is modulated by maternal nutrition during pregnancy. The dietary intake of linoleic acid (LA), an essential dietary n-6 polyunsaturated fatty acid (PUFA), has increased. We previously published that increased LA consumption during pregnancy does not alter offspring or placental weight but fetal plasma fatty acid composition the developing fetus obtains their required PUFA from the maternal circulation. However, it is unknown if increased maternal linoleic acid alters placental fatty acid storage, metabolism, transport, and general placental function. Female Wistar-Kyoto rats were fed either a low LA diet (LLA 1.44% of energy from LA) or high LA diet (HLA 6.21% of energy from LA) for 10 weeks before pregnancy and during gestation. Rats were sacrificed at embryonic day 20 (E20, term = 22 days) and placentae collected. The labyrinth of placentae from one male and one female fetus from each litter were analyzed. High maternal LA consumption increased placental total n-6 and LA concentrations, and decreased total n-3 PUFA, alpha-linolenic acid (ALA), and docosahexaenoic acid (DHA). Fatty acid desaturase 1 (Fads1), angiopoietin-like 4 (Angptl4), and diacylglycerol lipase beta (Daglb) mRNA were downregulated in placentae from offspring from HLA dams. Maternal high LA downregulated the fatty acid transport protein 4 (Fatp4) and glucose transporter 1 (Slc2a1) mRNA in placentae. IL-7 and IL-10 protein were decreased in placentae from offspring from HLA dams. In conclusion, a high maternal LA diet alters the placental fatty acid composition, inflammatory proteins, and expressions of nutrient transporters, which may program deleterious outcomes in offspring.
Publisher: BMJ
Date: 06-2021
Publisher: Wiley
Date: 02-06-2019
DOI: 10.1113/JP277583
Publisher: Elsevier BV
Date: 2020
Publisher: Wiley
Date: 30-10-2019
DOI: 10.1113/JP278473
Publisher: Elsevier BV
Date: 07-2019
Publisher: Cambridge University Press (CUP)
Date: 09-12-2020
DOI: 10.1017/S2040174419000813
Abstract: The endocannabinoid system (ECS), modulated by metabolites of linoleic acid (LA), is important in regulating cardiovascular function. In pregnancy, LA is vital for foetal development. We investigated the effects of elevated LA in H9c2 cardiomyoblasts in vitro and of a high linoleic acid (HLA, 6.21%) or low linoleic acid (LLA, 1.44%) diet during pregnancy in maternal and offspring hearts. H9c2 cell viability was reduced following LA exposure at concentrations between 300 and 1000 µM. HLA diet decreased cannabinoid receptor type 2 (CB 2 ) mRNA expression in foetal hearts from both sexes. However, HLA diet increased CB 2 expression in maternal hearts. The mRNA expression of fatty acid amide hydrolase (FAAH) in foetal hearts was higher in females than in males irrespective of diet and N-acyl phosphatidylethanolamine-specific phospholipase D (NAPE-PLD) mRNA expression showed an interaction between diet and sex. Data indicate that a high LA diet alters cell viability and CB 2 expression, potentially influencing cardiac function during pregnancy and development of the offspring’s heart.
Publisher: American Physiological Society
Date: 11-2020
DOI: 10.1152/AJPREGU.00214.2020
Abstract: Obesity is an increasing global health epidemic that affects all ages, including women of reproductive age. During pregnancy, maternal obesity is associated with adverse pregnancy outcomes that lead to complications for the mother. In addition, maternal obesity can increase the risk of poor perinatal outcomes for the infant due to altered development. Recent research has investigated the effects of maternal obesity on peripheral organ development and health in later life in offspring. In this review, we have summarized studies that investigated the programming effects of maternal obesity before and during pregnancy on metabolic, cardiovascular, immune, and microbiome perturbations in offspring. Epidemiological studies investigating the effects of maternal obesity on offspring development can be complex due to other copathologies and genetic ersity. Animal studies have provided some insights into the specific mechanisms and pathways involved in programming peripheral disease risk. The effects of maternal obesity during pregnancy on offspring development are often sex specific, with sex-specific changes in placental transport and function suggestive that this organ is likely to play a central role. We believe that this review will assist in facilitating future investigations regarding the underlying mechanisms that link maternal obesity and offspring disease risk in peripheral organs.
Publisher: Springer Science and Business Media LLC
Date: 18-07-2008
DOI: 10.1007/S00251-008-0316-0
Abstract: The major histocompatibility complex (MHC) is an essential part of the vertebrate immune response. MHC genes may be classified as classical, non-classical or non-functional pseudogenes. We have investigated the ersity of class I MHC genes in the brushtail possum, a marsupial native to Australia and an introduced pest in New Zealand. The MHC of marsupials is poorly characterised compared to eutherian mammal species. Comparisons between marsupials and eutherians may enhance understanding of the evolution and functions of this important genetic region. We found a high level of ersity in possum class I MHC genes. Twenty novel sequences were identified using polymerase chain reaction (PCR) primers designed from existing marsupial class I MHC genes. Eleven of these sequences shared a high level of homology with the only previously identified possum MHC class I gene TrvuUB and appear to be alleles at a single locus. Another seven sequences are also similar to TrvuUB but have frame-shift mutations or stop codons early in their sequence, suggesting they are non-functional alleles of a pseudogene locus. The remaining sequences are highly ergent from other possum sequences and clusters with American marsupials in phylogenetic analysis, indicating they may have changed little since the separation of Australian and American marsupials.
Publisher: Wiley
Date: 15-11-2020
DOI: 10.1113/JP280593
Publisher: CSIRO Publishing
Date: 2019
DOI: 10.1071/RD18436
Abstract: The 2018 edition of the Society for Reproductive Biology’s (SRB) Annual Meeting was a celebration of 50 years of Australian research into reproductive biology. The past 50 years has seen many important contributions to this field, and these advances have led to changes in practice and policy, improvements in the efficiency of animal reproduction and improved health outcomes. This conference review delivers a dedicated summary of the symposia, discussing emerging concepts, raising new questions and proposing directions forward. Notably, the symposia discussed in this review emphasised the impact that reproductive research can have on quality of life and the health trajectories of in iduals. The breadth of the research discussed encompasses the central regulation of fertility and cyclicity, life course health and how the environment of gametes and embryos can affect subsequent generations, significant advances in our understanding of placental biology and pregnancy disorders and the implications of assisted reproductive technologies on population health. The importance of a reliable food supply and protection of endangered species is also discussed. The research covered at SRB’s 2018 meeting not only recognised the important contributions of its members over the past 50 years, but also highlighted key findings and avenues for innovation moving forward that will enable the SRB to continue making significant contributions for the next 50 years.
Publisher: Frontiers Media SA
Date: 20-12-2019
Publisher: S. Karger AG
Date: 27-04-2016
DOI: 10.1159/000445112
Abstract: b i Objectives: /i /b A key problem in prenatal screening using extra-embryonic cells is the feasibility of extracting usable DNA from a small number of cells. Syncytial nuclear aggregates (SNAs) are multinucleated structures shed from the placenta. This study assesses the potential of SNAs as a source of fetal DNA for the detection of genetic abnormalities. b i Methods: /i /b SNAs were collected in vitro. Whole-genome lification was used to lify DNA from single SNAs, and DNA quality and quantity was assessed by spectrophotometry and PCR. Confocal microscopy was used to count nuclei within SNAs, determine metabolic activity and investigate DNA damage. Fetal sex and chromosomal/genetic abnormalities were investigated with array-comparative genomic hybridization (aCGH). b i Results: /i /b DNA was lified from 81% of the in idual SNAs. A mean of 61 ± 43 nuclei were found per SNA. DNA strand breaks were found in 76% of the SNAs. Seventy-five percent of SNAs yielded whole-genome- lified DNA of sufficient quality for aCGH after storage and shipping. In idual SNAs from the same pregnancy reliably gave the same chromosomal profile, and fetal sex and trisomies could be detected. A microdeletion was detected in one pregnancy. b i Conclusion: /i /b SNAs could provide a source of extra-embryonic DNA for the prenatal screening/diagnosis of fetal sex and chromosomal and sub-chromosomal genetic abnormalities.
Publisher: Springer Science and Business Media LLC
Date: 25-09-2019
DOI: 10.1038/S41598-019-50244-7
Abstract: Disease susceptibility of dairy cows is greatest during the transition from pregnancy to lactation. Circulating exosomes may provide biomarkers to detect at-risk cows to enhance health and productivity. From 490 cows, animals at high- (n = 20) or low-risk (n = 20) of transition-related diseases were identified using plasma non-esterified fatty acid and β-hydroxybutyrate concentrations and liver triacylglyceride concentrations during the two weeks post-calving. We isolated circulating exosomes from plasma of dairy cows at low-risk (LR-EXO) and high-risk (HR-EXO), and analyzed their proteome profiles to determine markers for metabolic dysfunction. We evaluated the effects of these exosomes on eicosanoid pathway expression by bovine endometrial stromal (bCSC) and epithelial (bEEL) cells. HR-EXO had significantly lower yield of circulating exosomes compared with LR-EXO, and unique proteins were identified in HR-EXO and LR-EXO. Exposure to LR-EXO or HR-EXO differentially regulated eicosanoid gene expression and production in bCSC and bEEL cells. In bCSC, LR-EXO exposure increased PGE 2 and PGD 2 production, whereas HR-EXO exposure increased PTGS2 gene expression. In bEEL, HR-EXO exposure caused a decrease in PGE 2, PGF 2α , PGD 2 , PGFM and TXB 2 production. The unique presence of serpin A3-7, coiled-coil domain containing 88A and inhibin/activin β A chain in HR-EXO, indicates potential biomarkers for cows at-risk for metabolic diseases. Our results are in line with the health status of the cow indicating a potential diagnostic role for exosomes in enhancing cows’ health and fertility.
No related grants have been discovered for Olivia Holland.