- Pregnancy and preeclampsia studies
- Birth, Development, and Health
- Gestational Diabetes Research and Management
- Neonatal Respiratory Health Research
- Prenatal Screening and Diagnostics
- Vitamin D Research Studies
- Pregnancy and Medication Impact
- Reproductive System and Pregnancy
- Extracellular vesicles in disease
- Endometriosis Research and Treatment
- Epigenetics and DNA Methylation
- Neonatal and fetal brain pathology
- Genetic Syndromes and Imprinting
- MicroRNA in disease regulation
- Infant Nutrition and Health
- RNA modifications and cancer
- Drug Transport and Resistance Mechanisms
- Diet and metabolism studies
- Renal and related cancers
- Bone health and osteoporosis research
- Assisted Reproductive Technology and Twin Pregnancy
- Adipose Tissue and Metabolism
- Neonatal Health and Biochemistry
- Molecular Biology Techniques and Applications
- Gynecological conditions and treatments
University of Southampton
2015-2024
Southampton General Hospital
2008-2022
University of Auckland
1976-2022
Wilhelmina Children's Hospital
2016
Institute of Developmental Physiology
2011
Cambridge University Press
2010-2011
New York University Press
2010-2011
Chitose Institute of Science and Technology
2010-2011
John Radcliffe Hospital
2011
International Society for Developmental Origins of Health and Disease
2006-2010
Early embryonic development is known to be susceptible maternal undernutrition, leading a disease‐related postnatal phenotype. To determine whether this sensitivity extended into oocyte development, we examined the effect of normal protein diet (18% casein; NPD) or isocaloric low (9% LPD) restricted one ovulatory cycle (3.5 days) prior natural mating in female MF‐1 mice. After mating, all females received NPD for remainder gestation and offspring were litter size adjusted fed standard chow....
Pregnancy 25-hydroxyvitamin D [25(OH)D] concentrations are associated with maternal and fetal health outcomes. Using physiological human placental perfusion villous explants, we investigate the role of placenta in regulating relationships between 25(OH)D physiology. We demonstrate active uptake
The placenta is a fast-evolving organ with large morphological and histological differences across eutherians, but the genetic changes driving placental evolution have not been fully elucidated. Transposable elements, through their capacity to quickly generate variation affect host gene regulation, may helped define species-specific trophoblast expression programs. Here we assess contribution of transposable elements human as enhancers or promoters. Using epigenomic data from primary...
The early life environment has long-term implications for the risk of developing cardiovascular (CV) disease in adulthood. Fetal responses to changes maternal nutrition may be immediate benefit fetus, but effects these adaptations prove detrimental if postnatal does not match that predicted by fetus on basis its prenatal environment. We tested this predictive adaptive response hypothesis with respect CV function sheep. observed a mismatch between pre- and nutrient environments induced an...
Fetal growth depends on placental transfer of amino acids from maternal to fetal blood. The mechanisms net acid efflux across the basal membrane (BM) syncytiotrophoblast fetus, although vital for transport, are poorly understood. We examined hypothesis that facilitated diffusion by transporters TAT1, LAT3 and LAT4 plays an important role in this process, with possible effects growth. Amino was measured isolated perfused human cotyledons (n = 5 per experiment) using techniques which...
Environmental perturbations during early mammalian development can affect aspects of offspring growth and cardiovascular health. We have demonstrated previously that maternal gestational dietary protein restriction in mice significantly elevated adult systolic blood pressure. Therefore, the present study investigates key mechanisms pressure regulation these mice. Following mating, female MF-1 were assigned to either a normal-protein diet (NPD; 18 % casein) or an isocaloric low-protein...
We have previously demonstrated inverse associations between maternal 25(OH)-vitamin D status and perinatal DNA methylation at the retinoid-X-receptor-alpha (RXRA) locus RXRA offspring bone mass. In this study, we used an existing randomized trial to test hypothesis that gestational vitamin supplementation would lead reduced methylation. The Maternal Vitamin Osteoporosis Study (MAVIDOS) was a multicenter, double-blind, randomized, placebo-controlled of 1000 IU/day cholecalciferol or matched...
Transfer of glucose across the human placenta is directly proportional to maternal concentrations even when these are well above physiological range. This study investigates relationship between and fetal transfer placenta. d-glucose, 3H-3-o-methyl-d-glucose (3H-3MG) 14C-l-glucose isolated perfused placental cotyledon was determined for arterial d-glucose 0 20 mmol/l. Clearance 3H-3MG or not affected by in either circulation. Based on reported KM GLUT1, would be expected show signs...
Both maternal 25-hydroxyvitamin D (25(OH)D) concentrations during pregnancy and placental amino acid transporter gene expression have been associated with development of the offspring in terms body composition bone structure. Several genes vitamin response elements their promoters suggesting possible linkage these two mechanisms. We aimed to establish whether 25(OH)D D-binding protein (VDBP) levels relate transporters. RNA was extracted from 102 samples collected Southampton Women's Survey,...
Intrahepatic cholestasis of pregnancy (ICP) causes increased transfer maternal bile acids to the fetus and an incidence sudden fetal death. Treatment includes ursodeoxycholic acid (UDCA), but it is not clear if UDCA protects fetus. This study explores placental transport taurocholate (TC) by organic anion–transporting polypeptide, (OATP)4A1, its effects on proteome vascular function, how these are modified UDCA. Various methodological approaches including villous fragments Xenopus laevis...
The early-life environment affects risk of later metabolic disease, including glucose intolerance, insulin resistance and obesity. Changes in hypothalamo-pituitary-adrenal (HPA) axis sympathoadrenal function may underlie these disorders. To determine consequences undernutrition early gestation and/or immediately following weaning on HPA function, 2- to 3-year-old Welsh Mountain ewes received 100% (C, n = 39) or 50% nutritional requirements (U, 41) from 1-31 days gestation, thereafter. From...
ABSTRACT: Twenty‐eight elderly volunteers of the 65+ age group and 28 control subjects 20–40 each received a single oral dose (1 gm) acetaminophen in powder form. The plasma level was measured over 6 hours. Plasma half‐life, clearance relative volume distribution drug were calculated. Within there wide (threefold) range half‐life rate, with great deal overlap between two groups. However, for elderly, mean 2.17 hours, significantly longer than young (1.75 hours). rate slower (.254 .340...
The nutritional environment during development and even prior to conception may contribute cardiovascular risk. In mature adult female sheep, we investigated the effect of preconceptional periconceptional maternal restriction on vascular reactivity arteries from four beds supplying heart, thorax, kidney hindlimb. Welsh Mountain ewes received 100% nutrient requirements throughout gestation (control group, C, n = 18), or 50% for 30 days (preconceptional PRE, 20) 15 either side...
Introduction Maternal environment and lifestyle factors may modify placental function to match the mother's capacity support demands of fetal growth. Much remains be understood about maternal influences on metabolic amino acid transporter gene expression. We investigated body composition (e.g. fat muscle content) a selection genes their associations with Methods RNA was extracted from 102 term Southampton Women's Survey samples. Expression nine metabolic, seven exchange, eight accumulative...
Fetal growth is dependent on both the quantity and relative composition of amino acids delivered to fetal circulation, impaired placental acid supply associated with restricted growth. Amino exchangers can alter composition, but not quantity, in intra- extracellular pools. In placenta, may be important determinants circulation. This study investigates substrate specificity exchange between placenta feto-placental Maternal-fetal transfer radiolabelled creatinine were measured isolated...
Abstract Placental function is essential for fetal development and establishing the foundations lifelong health. The placental villous stroma a connective tissue layer that supports capillaries trophoblast. All nutrients cross placenta must also stroma, yet little known about this region. This study uses high‐resolution three‐dimensional imaging to explore structural complexity of region within villi. Serial block‐face scanning electron microscopy confocal were used image in...