A5053089649- Birth, Development, and Health
- Pregnancy and preeclampsia studies
- Neonatal Respiratory Health Research
- Congenital heart defects research
- Gestational Diabetes Research and Management
- Reproductive Biology and Fertility
- Assisted Reproductive Technology and Twin Pregnancy
- Congenital Diaphragmatic Hernia Studies
- Neonatal and fetal brain pathology
- Adipose Tissue and Metabolism
- Mitochondrial Function and Pathology
- Cancer-related molecular mechanisms research
- Anesthesia and Neurotoxicity Research
- Cardiovascular Function and Risk Factors
- RNA modifications and cancer
- MicroRNA in disease regulation
- Diet and metabolism studies
- Maternal and fetal healthcare
- Neuroscience of respiration and sleep
- Renal and related cancers
- Infant Nutrition and Health
- Animal Genetics and Reproduction
- Peroxisome Proliferator-Activated Receptors
- Ultrasound and Hyperthermia Applications
- Obesity and Health Practices
University of Cambridge
2015-2025
University of South Australia
2011-2024
University College London
2023
Ulverscroft (United Kingdom)
2020
Cancer Research UK Cambridge Center
2019
The University of Adelaide
2007-2018
Addenbrooke's Hospital
2018
Bridge University
2016
Placental insufficiency, resulting in restriction of fetal substrate supply, is a major cause intrauterine growth (IUGR) and increased neonatal morbidity. Fetal adaptations to placental maintain the key organs, including heart, but impact these on individual cardiomyocytes unknown. hence was induced sheep by removing majority caruncles ewe before mating (placental restriction, PR). Vascular surgery performed 13 control 11 PR fetuses at 110–125 days gestation (term: 150 ± 3 days). with mean...
Experimental studies that are relevant to human pregnancy rely on the selection of appropriate animal models as an important element in experimental design. Consideration strengths and weaknesses any model disease is fundamental effective meaningful translation preclinical research. Studies sheep have made significant contributions our understanding normal abnormal development fetus. As a pregnancy, enabled scientists clinicians answer questions about etiology treatment poor maternal,...
Abstract Over 30 years ago Professor David Barker first proposed the theory that events in early life could explain an individual's risk of non‐communicable disease later life: developmental origins health and (DOHaD) hypothesis. During 1990s validity DOHaD hypothesis was extensively tested a number human populations mechanisms underpinning it characterised range experimental animal models. past decade, researchers have sought to use this mechanistic understanding develop therapeutic...
Placental insufficiency is the leading cause of intrauterine growth restriction in developed world and results chronic hypoxemia fetus. Oxygen essential for fetal heart development, but a hypoxemic environment utero can permanently alter development cardiomyocytes. The present study aimed to investigate effect placental on total number cardiomyocytes, cardiomyocyte apoptosis, length coronary capillaries, expression genes regulated by hypoxia.We induced experimental from conception, which...
Abstract The mechanisms that drive placental dysfunction in pregnancies complicated by hypoxia and fetal growth restriction remain poorly understood. Changes to mitochondrial respiration contribute cellular conditions of have been implicated the pathoaetiology pregnancy complications, such as pre‐eclampsia. We used bespoke isobaric hypoxic chambers a combination functional, molecular imaging techniques study metabolism dynamics sheep undergoing pregnancy. show triggers shift capacity away...
Reduced growth in fetal life together with accelerated childhood, results a ~50% greater risk of coronary heart disease adult life. It is unclear why changes patterns body and early can lead to an increased cardiovascular adulthood. We aimed investigate the role insulin-like factors growth-restricted fetus lamb. Hearts were collected from control placentally restricted (PR) fetuses at 137-144 days gestation average (ABW) low (LBW) birth weight lambs 21 age. quantified cardiac mRNA expression...
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.
Preeclampsia continues to be a prevalent pregnancy complication and underlying mechanisms remain controversial. A common feature of preeclampsia is utero-placenta hypoxia. In contrast the impact hypoxia on placenta fetus, comparatively little known about maternal physiology.We adopted an integrative approach investigate inter-relationship between chronic during with maternal, placental, fetal outcomes, in preeclampsia. We exploited novel technique using isobaric hypoxic chambers vivo...
Intrauterine growth restriction (IUGR) increases the risk of ischemic heart disease in adulthood. Studies rats suggest cardiac vulnerability is more pronounced males and offspring that were exposed to hypoxia utero. Therefore, we aimed test hypotheses 1) IUGR adolescent males, but not females, have fewer cardiomyocytes altered expression cardiometabolic genes compared with controls; 2) due has a greater effect on these parameters nutrient restriction. was induced guinea pigs by maternal (MH;...
Experimental studies in animal models supporting protective effects on the fetus of melatonin adverse pregnancy have prompted clinical trials human complicated by fetal growth restriction. However, defense to acute hypoxia, such as that which may occur during labor, remain unknown. This translational study tested hypothesis, vivo, modulates cardiometabolic responses hypoxia chronically instrumented late gestation sheep via alterations nitric oxide (NO) bioavailability. Under anesthesia, 6 at...
Placental restriction and insufficiency are associated with altered patterns of placental growth, morphology, substrate transport capacity, growth factor expression, glucocorticoid exposure. We have used a pregnant sheep model in which the intrauterine environment has been perturbed by uterine carunclectomy (Cx). This procedure results early either development chronic fetal hypoxemia (PaO2≤17 mmHg) late gestation or compensatory maintenance normoxemia (PaO2>17 mmHg). Based on PaO2, Cx,...
Experimental placental restriction (PR) by carunclectomy in fetal sheep results intrauterine growth (IUGR), chronic hypoxemia, increased plasma cortisol, and decreased lung surfactant protein (SP) expression. The mechanisms responsible for SP expression are unknown but may involve glucocorticoid (GC) action or changes hypoxia signaling. Endometrial caruncles were removed from nonpregnant ewes to induce PR. Lungs collected control PR fetuses at 130-135 (n = 19) 139-145 28) days of gestation....
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...
High-intensity focused ultrasound can ablate blood flow in the sheep placenta and may be translatable to human twin-twin transfusion syndrome.
Abstract Chronic fetal hypoxaemia is a common pregnancy complication that increases the risk of infants experiencing respiratory complications at birth. In turn, chronic promotes oxidative stress, and maternal antioxidant therapy in animal models hypoxic has proven to be protective with regards growth cardiovascular development. However, whether antenatal confers any benefit on lung development complicated pregnancies not yet been investigated. Here, we tested hypothesis treatment MitoQ will...
Activation of the insulin-like growth factor-1 receptor (IGF-1R) is known to play a role in cardiomyocyte hypertrophy. While IGF-2R understood be clearance for IGF-2, there also evidence that it may induction pathological It not whether activates hypertrophy during fetal heart. Fetal sheep hearts (125 ± 0.4 days gestation) were dissected, and cardiomyocytes isolated from left right ventricles culturing. Cultured treated with either LONG R(3)IGF-1, an IGF-1R agonist; picropodophyllin,...