A5073921107- Birth, Development, and Health
- Neonatal Respiratory Health Research
- Pregnancy and preeclampsia studies
- Diet and metabolism studies
- Neonatal and fetal brain pathology
- Infant Nutrition and Health
- Estrogen and related hormone effects
- Climate Change and Health Impacts
- Adipose Tissue and Metabolism
- Fatty Acid Research and Health
- Gestational Diabetes Research and Management
- Neuroscience of respiration and sleep
- Endometrial and Cervical Cancer Treatments
- Congenital Diaphragmatic Hernia Studies
- Lipoproteins and Cardiovascular Health
- Vitamin C and Antioxidants Research
- Diet, Metabolism, and Disease
- Anesthesia and Neurotoxicity Research
- NF-κB Signaling Pathways
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Heart Rate Variability and Autonomic Control
- Lipid metabolism and disorders
- Non-Invasive Vital Sign Monitoring
- Mitochondrial Function and Pathology
University of Cambridge
2014-2025
Kings Health Partners
2018-2022
King's College London
2018-2022
Ulverscroft (United Kingdom)
2020
Centre for Inflammation Research
2020
Queen's Medical Centre
2020
University of Edinburgh
2020
Addenbrooke's Hospital
2017
Bridge University
2016
Chronic fetal hypoxia is commonly associated with growth restriction and can predispose to respiratory disease at birth in later life. Antenatal antioxidant treatment has been investigated overcome the effects of oxidative stress utero improve outcomes. We aimed determine if chronic antenatal administration persist lung early adulthood. Chronically catheterised pregnant sheep were exposed normoxia (N; n = 20) or (H; 18; 10% O2) ± maternal daily i. v. saline (N 11; H 8) Vitamin C (VC; NVC 9;...
Key points The in vivo fetal cardiovascular defence to chronic hypoxia has remained by and large an enigma because no technology been available induce significant prolonged whilst recording longitudinal changes regional blood flow as the hypoxic pregnancy is developing. We introduce a new technique able maintain chronically instrumented maternal sheep preparations under isobaric for most of gestation, beyond levels that can be achieved high altitude relevance magnitude human intrauterine...
Evidence derived from human clinical studies and experimental animal models shows a causal relationship between adverse pregnancy increased cardiovascular disease in the adult offspring. However, translational isolating mechanisms to design intervention are lacking. Sheep humans share similar precocial developmental milestones anatomy physiology. We tested hypothesis sheep that maternal treatment with antioxidants protects against fetal growth restriction programmed hypertension adulthood...
Mitochondrial therapy may cure hypertension in adult offspring of complicated pregnancies.
Progress in the study of pregnancy complicated by chronic hypoxia large mammals has been held back inability to measure long-term significant reductions fetal oxygenation at values similar those measured human growth restriction. Here, we introduce a technique for physiological research able maintain chronically instrumented maternal and sheep prolonged periods gestation under controlled isolated beyond levels that can be achieved habitable high altitude. This model permits measurement...
There is a search for rescue therapy against fetal origins of cardiovascular disease in pregnancy complicated by chronic hypoxia, particularly following clinical diagnosis growth restriction (FGR). Melatonin protects the placenta adverse pregnancy; however, whether melatonin heart and vasculature hypoxic independent effects on unknown. Whether can dysfunction when treatment commences FGR also We isolated developing system chick embryo during incubation. tested hypothesis that directly...
Abstract Background Chronic hypoxemia is a common cause of fetal growth restriction and can have significant effects on the developing lung. Maternal antioxidant treatment in hypoxic pregnancy protects against offspring cardiovascular dysfunction. The antenatal antioxidants lung development chronically restricted fetus unknown. Methods We investigated effect maternal daily Vitamin C (200 mg/kg i.v. vs. Saline) for month late gestation molecular markers regulating maturation between normoxic...
Key points Fetal heart rate variability (FHRV) has long been recognised as a powerful predictor of fetal wellbeing, and decrease in FHRV is associated with compromise. However, the mechanisms by which reduced chronically hypoxic fetus have yet to be established. The sympathetic parasympathetic influences on mature at different rates throughout life, can assessed time domain power spectral analysis FHRV. In this study instrumented sheep late gestation, we analysed daily over 16 day period...
Common complications of pregnancy, such as chronic fetal hypoxia, trigger a origin cardiovascular dysfunction and programme disease in later life. Sildenafil treatment protects placental perfusion growth, but whether the effects sildenafil transcend placenta to affect fetus is unknown. Using chick embryo model, here we show that directly system hypoxic development, mechanisms protection include reduced oxidative stress increased nitric oxide bioavailability; does not protect against growth...
Maternal obesity (MO) causes maternal and fetal oxidative stress (OS) metabolic dysfunction. We investigated whether supplementing obese mothers with resveratrol improves alterations reduces OS in the placenta liver. From weaning through pregnancy female Wistar rats ate chow (C) or a high-fat diet (MO). One month before mating until 19 days' gestation (dG), half received 20 mg resveratrol/kg/d orally (Cres MOres). At 19dG, body weight, retroperitoneal fat adipocyte size, parameters,...
Chronic fetal hypoxaemia is a common pregnancy complication associated with intrauterine growth restriction that may influence respiratory outcome at birth. We investigated the effect of maternal chronic hypoxia for month in late gestation on signalling pathways regulating lung maturation and transition to air-breathing birth using isobaric hypoxic chambers without alterations food intake. Maternal increases expression genes signalling, liquid reabsorption surfactant maturation, which be an...
The hypoxic fetus is at greater risk of cardiovascular demise during a challenge, but the reasons behind this are unknown. Clinically, progress has been hampered by inability to study human non-invasively for long period gestation. Using experimental animals, there also an induce gestational hypoxia while recording fetal function as pregnancy occurring. We use novel technology in sheep that combines induction controlled chronic with simultaneous, wireless blood pressure and flow signals from...
In the fetus, appropriate balance of prooxidants and antioxidants is essential to negate detrimental effects oxidative stress on lung maturation. Antioxidants improve respiratory function in postnatal life adulthood. However, outcomes biological mechanisms antioxidant action fetal are unknown.
Abstract Antenatal glucocorticoids accelerate fetal lung maturation and reduce mortality in preterm babies but can trigger adverse effects on the cardiovascular system. The mechanisms underlying off‐target of synthetic mostly used, Dexamethasone (Dex) Betamethasone (Beta), are unknown. We investigated Dex Beta structure function, molecular mechanism using chicken embryo, an established model system to isolate therapy developing heart vasculature, independent mother or placenta. Fertilized...
In mammals, pregnancy complicated by chronic hypoxia can program hypertension in the adult offspring. However, mechanisms remain uncertain because partial contributions of challenge on placenta, mother, and fetus are difficult to disentangle. Here, we used chicken embryo—an established model system that permits isolation direct effects developmental cardiovascular offspring, independent additional mother or placenta. Fertilized eggs were exposed normoxia (N; 21% O 2 ) (H; 13.5%–14% from...
The use of statins in complicated pregnancy is being considered, as they protect endothelial function the mother and placenta. However, whether affect cardiovascular fetus completely unknown. Here, we have determined effects pravastatin underlying mechanisms on system hypoxic chicken embryo, a model that permits direct developing offspring to be isolated independently additional and/or Chicken embryos were incubated under normoxia or hypoxia (14% O2 ) from day 1 ± (1 mg/kg/d) 13 incubation...
Endometrial cancer is a common gynaeological malignancy: life time exposure to oestrogen key risk factor. Oestrogen action mediated by receptors encoded ESR1 (ERα) and ESR2 (ERβ): ERα plays role in regulating endometrial cell proliferation. A truncated splice variant isoform (ERβ5) highly expressed cancers. This study explored whether ERβ5 alters responsiveness of epithelial cells. Immunhistochemistry profiling human tissue biopsies identified cells co-expressing stage I adenocarcinomas post...
Antenatal glucocorticoid therapy reduces mortality in the preterm infant, but evidence suggests off-target adverse effects on developing cardiovascular system. Whether deleterious are direct offspring or secondary to alterations uteroplacental physiology is unclear. Here, we isolated of glucocorticoids using chicken embryo, a model system which heart and circulation can be investigated, independent mother and/or placenta. Fertilized eggs were incubated divided randomly into control (C)...
Abstract It is now well accepted that exposure to adverse environmental conditions in utero can predispose a fetus disease later life. Using an avian model study the programming of has unique advantage as it allows isolation direct effects on fetal physiology, without any confounding via mother or placenta. However, experiments models are limited by lack well-established surgical protocols for adult bird, which we have established this study. Surgery was performed seven young Bovan Brown...