Early pregnancy weight gain and fat accrual predict pregnancy outcome in growing adolescent sheep

Funding: This work was funded by the Scottish Government’s Rural and Environment Science and Analytical Services Division. Author contribution statement: JW developed the animal model, performed experiments, analysed the data and wrote the paper. RA and JM performed experiments and conducted the laboratory analysis. Acknowledgements: Dr Graham Horgan (Biomathematics and Statistics Scotland) provided statistical advice and Dr Clare Adam gifted the leptin antibody.Peer reviewedPostprin

Ovine prenatal growth-restriction and sex influence fetal adipose tissue phenotype and impact postnatal lipid metabolism and adiposity in vivo from birth until adulthood

Funding: This work was funded by the Scottish Government’s Rural and Environmental Science and Analytical Services Division (RESAS) including the Strategic Partnership for Animal Science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Undernutrition and stage of gestation influence fetal adipose tissue gene expression

Funded by the Scottish Government’s Rural and Environment Science and Analytical Services Division (RESAS), including the Strategic Partnership for Animal Science Excellence (SPASE) and the U.S. National Institutes of Health (HD045784). None of the authors had any financial or personal conflicts of interest.Peer reviewedPostprin

Perinatal complications and maximising lamb survival in an adolescent paradigm characterised by premature delivery and low birthweight

Acknowledgments Dr Anja Petrie provided supporting veterinary input in her role as Named Veterinary Surgeon. Funding acquisition: Jacqueline M. Wallace.Peer reviewedPublisher PD

An immunohistochemical study of the localization and developmental expression of ghrelin and its functional receptor in the ovine placenta

<p>Abstract</p> <p>Background</p> <p>Ghrelin is an orexigenic hormone principally produced by the stomach, but also by numerous peripheral tissues including the placenta. Ghrelin acts via growth hormone secretagogue receptors (GHSR-1a) to alter food intake, fat utilization, and cellular proliferation, and has been suggested to play a role in the developmental growth of the fetoplacental unit. The placental expression of ghrelin and its role in ruminant species is not known. We tested the hypotheses that ghrelin and its functional receptor, GHSR-1a, are present in tissues of the ovine placenta, and that their expression is linked to the stage of development.</p> <p>Methods</p> <p>Antibodies raised against ghrelin and GHSR-1a were used in standard immunohistochemical protocols on placental tissues collected from pregnant ewes (n = 6 per gestational time point) at days 50, 80, 100, 128 and 135 of gestation (term ≈ day 145). Immunostaining for ghrelin and GHSR-1a was quantified using computer-aided image analysis. Image analysis data were subjected to one-way ANOVA, with differences in immunostaining between time-points determined by Fisher's least significant difference.</p> <p>Results</p> <p>Positive immunostaining for ghrelin was detected in ovine placentae at all gestational time points, with staining localized to the maternal epithelium, caruncle and trophectoderm. There was a significant effect of gestational age (p < 0.001) on the placental expression of ghrelin, with maximal levels at gestational day 80. GHSR-1a immunostaining was detected in the fetal trophectoderm at all time points. In contrast to the gestational pattern of ghrelin expression, there was no effect of gestational age on placental GHSR-1a immunoexpression.</p> <p>Conclusion</p> <p>Ghrelin and GHSR-1a are both present in the ovine placenta, and ghrelin displays a developmentally-related pattern of expression. Therefore, these data strongly suggest that the ghrelin system may have a role in feto-placental development in sheep.</p

Peri- and postnatal effects of prenatal adenoviral VEGF gene therapy in growth-restricted sheep

Supported by Wellcome Trust project grant 088208 to A.L.D., J.M.W., D.M.P., I.C.Z., and J.F.M. Wellbeing of Women research training fellowship 318 to D.J.C., Scottish Government work package 4.2 to J.M.W., J.S.M., and R.P.A., as well as funding from the National Institute for Health Research University College London Hospitals Biomedical Research Centre A.L.D. and D.M.P., the British Heart Foundation to I.C.Z., and Ark Therapeutics Oy, Kuopio, Finland, which supplied adenovirus vectors free of charge.Peer reviewedPublisher PD

Ovine prenatal growth restriction impacts glucose metabolism and body composition throughout life in both sexes

Peer reviewedPostprin

The expression of ovine placental lactogen, StAR and progesterone-associated steroidogenic enzymes in placentae of overnourished growing adolescent ewes.

Overnourishing pregnant adolescent sheep promotes maternal growth but reduces placental mass, lamb birth weight and circulating progesterone. This study aimed to determine whether altered progesterone reflected transcript abundance for StAR (cholesterol transporter) and the steroidogenic enzymes (Cyp11A1, Hsd3b and Cyp17). Circulating and placental expression of ovine placental lactogen (oPL) was also investigated. Adolescent ewes with singleton pregnancies were fed high (H) or moderate (M) nutrient intake diets to restrict or support placental growth. Experiment 1: peripheral progesterone and oPL concentrations were measured in H (n=7) and M (n=6) animals across gestation (days 7-140). Experiment 2: progesterone was measured to mid- (day 81; M: n=11, H: n=13) or late gestation (day 130; M: n=21, H: n=22), placental oPL, StAR and steroidogenic enzymes were measured by qPCR and oPL protein by immunohistochemistry. Experiment 1: in H vs M animals, term placental (

The evolving paleobathymetry of the circum-Antarctic Southern Ocean since 34 Ma – A key to understanding past cryosphere-ocean developments

The Southern Ocean is a key player in the climate, ocean and atmospheric system. As the only direct connection between all three major oceans since the opening of the Southern Ocean gateways, the development of the Southern Ocean and its relationship with the Antarctic cryosphere has influenced the climate of the entire planet. Although the depths of the ocean floor have been recognized as an important factor in climate and paleoclimate models, appropriate paleobathymetric models including a detailed analysis of the sediment cover are not available. Here, we utilize more than 40 years of seismic reflection data acquisition along the margins of Antarctica and its conjugate margins, along with multiple drilling campaigns by the International Ocean Discovery Program (IODP) and its predecessor programs. We combine and update the seismic stratigraphy across the regions of the Southern Ocean and calculate ocean-wide paleobathymetry grids via a backstripping method. We present a suite of high-resolution paleobathymetric grids from the Eocene-Oligocene Boundary to modern times. The grids reveal the development of the Southern Ocean from isolated basins to an interconnected ocean affected by the onset and vigor of an Antarctic Circumpolar Current, as well as the glacial sedimentation and erosion of the Antarctic continent. The ocean-wide comparison through time exposes patterns of ice sheet development such as switching of glacial outlets and the change from wet-based to dry-based ice sheets. Ocean currents and bottom-water production interact with the sedimentation along the continental shelf and slope and profit from the opening of the ocean gateways

Telehealth cancer-related fatigue clinic model for cancer survivors: A pilot randomised controlled trial protocol (the T-CRF trial)

INTRODUCTION: Cancer-related fatigue (CRF) is one of the most common and debilitating adverse effects of cancer and its treatment reported by cancer survivors. Physical activity, psychological interventions and management of concurrent symptoms have been shown to be effective in alleviating CRF. This pilot randomised controlled trial (RCT) will determine the feasibility of a telehealth CRF clinic intervention (T-CRF) to implement evidence-based strategies and assess the impact of the intervention on CRF and other clinical factors in comparison to usual care. METHODS AND ANALYSIS: A parallel-arm (intervention vs usual care) pilot RCT will be conducted at the Princess Alexandra Hospital in Queensland, Australia. Sixty cancer survivors aged 18 years and over, who report moderate or severe fatigue on the Brief Fatigue Inventory and meet other study criteria will be recruited. Participants will be randomised (1:1) to receive the T-CRF intervention or usual care (ie, specialist-led care, with a fatigue information booklet). The intervention is a 24-week programme of three telehealth nurse-led consultations and a personalised CRF management plan. The primary objective of this pilot RCT is to determine intervention feasibility, with a secondary objective to determine preliminary clinical efficacy. Feasibility outcomes include the identification of recruitment methods; recruitment rate and uptake; attrition; adherence; fidelity; apathy; and intervention functionality, acceptability and satisfaction. Clinical and resource use outcomes include cancer survivor fatigue, symptom burden, level of physical activity, productivity loss, hospital resource utilisation and carer\u27s fatigue and productivity loss. Descriptive statistics will be used to report on feasibility and process-related elements additional to clinical and resource outcomes. ETHICS AND DISSEMINATION: This trial is prospectively registered (ACTRN12620001334998). The study protocol has been approved by the Metro South Health and Hospital Services Human Research Ethics Committee (MSHHS HREC/2020/QMS/63495). Findings will be disseminated through peer-reviewed publications, national and international conferences and seminars or workshops. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry ID: ACTRN12620001334998; Pre-results. Trial Version: Version 1.1. Last updated 10 December 2020