Research
My research interests are in comparative developmental physiology with particular emphasis on the endocrine and other mechanisms controlling intrauterine development and its long-term, postnatal consequences. My long term goal is to identify how conditions during early life programme development and increase susceptibility to adult-onset degenerative diseases, such as Type 2 diabetes and metabolic syndrome. The research takes an integrated approach from the systems to the molecular levels and has both basic and strategic aims with direct applications to medicine, veterinary medicine and the food and livestock industries. My research has three main themes.
Feto-placental growth and metabolism
Lately, we have been focusing on the role of the placenta in developmental programming and the use of tracer methodology to measure unidirectional and net rates of placental nutrient transfer during different nutritional and endocrine conditions. Together with analyses of tissue morphology, enzyme activities and expression of growth and gluco-regulatory genes, these measurements provide a comprehensive assessment of the environmental factors controlling feto-placental growth and metabolism. These studies have shown that fetal hormones and growth factors, like cortisol and the insulin-like growth factors, can influence the placental supply and fetal utilization of nutrients and, hence, lead to intrauterine programming. Currently, we are examining how the placenta transmits memories of early events to intrauterine tissues later in development.
Feto-placental maturation
Hormonal control of tissue maturation is one of the major research interests of my group. More specifically, we have been examining the role of glucocorticoids as maturational and programming signals. In addition, the cellular and molecular mechanisms by which glucocorticoids act to permanently alter tissue structure and function are being investigated. In particular, we are examining the ontogeny and endocrine regulation of mitochondrial function in fetal and placental tissues and the role of these early life developmental processes in programming of adult metabolism.
Postnatal consequences of intrauterine programming
In recent years, we have begun to assess the postnatal physiological consequences of altered patterns of intrauterine development. We have shown that environmentally-induced changes in prenatal growth determine postnatal growth, fat deposition, glucose metabolism and the function of several endocrine systems including the pancreas, pituitary, adrenal and adipose tissue. Our studies have used a range of approaches to manipulate the intrauterine environment including embryo transfer, dietary manipulation, hormone administration and multiple pregnancy. Currently, we are examining the postnatal metabolic and behavioural consequences of maternal obesity and stress during pregnancy.
Main funding: BBSRC, Horserace Betting Levy Board, MRC
Collaborators
Professor Graham Burton
Dr Emily Camm
Dr Miguel Constancia
Ms Katie Davies
Dr Alison Forhead
Professor Dino Giussani
Professor Sean Limesand
Dr Andrew Murray
Professor Sue Ozanne
Professor Gordon Smith
Dr Amanda Sferruzzi-Perri
Dr Owen Vaughan
Publications
Sferruzzi-Perri AN, Higgins JS, Vaughan OR, Murray AJ, Fowden AL, (2019), Placental mitochondria adapt developmentally and in response to hypoxia to support fetal growth, PNAS 116 1621-1626
Vaughan OR, De Blasio MJ, Fowden AL, (2018), Ovine uteroplacental and fetal metabolism during and after cortisol overexposure in late gestation, Am J Physiol 314 R791-R801
De Blasio MJ, Lanham S, Blache D, Oreffo R, Fowden AL, Forhead AJ, (2018), Sex- and bone-specific responses in bone structure to exogenous leptin and leptin receptor antagonism in the ovine fetus, Am J Physiol 314 R781-R790
Sferruzzi-Perri AN, Sandovici I, Constancia M, Fowden AL, (2017), Placental phenotype and the insulin-like growth factors: resource allocation to fetal growth, J Physiol 595 5057-5093
Franko KL, Forhead AJ, Fowden AL, (2017), Effects of stress during pregnancy on hepatic glucogenic capacity of rat dams and their fetuses, Physiol Rep. 5 e13293
Valenzuela OA, Jellyman JK, Allen VL, Holdstock NB, Fowden AL, (2017), Effects of maternal dexamethasone treatment on pancreatic β cell function in the pregnant mare and postnatal foal, Equine Vet J 49 99-106
Harris S, De Blasio MJ, Davis M, Kelly A, Davenport H, Wooding FBP, Blanche D, Meredith D, Anderson M, Fowden AL, Limesand S, Forhead AJ, (2017), Hypothyroidism in utero stimulates pancreatic beta cell proliferation and hyperinsulinaemia in the ovine fetus during late gestation, J Physiol 595 3331-2243
Fowden AL, Valenzuela OA, Vaughan OR, Jellyman JK, Forhead AJ, (2016), Glucocorticoid programming of intrauterine development, Dom Anim Endocrinol 56 Suppl. S121-S131
Vaughan OR, Fowden AL, (2016), Placental metabolism: substrate requirements and the response to stress, Reprod Dom Anim 51 (Suppl 2) 25-35
Musial B, Fernandez-Twinn DS, Vaughan OR, Ozanne SE, Voshol P, Sferruzzi-Perri AN, Fowden AL, (2016), Proximity to delivery alters insulin sensitivity and glucose metabolism in pregnant mice, Diabetes 65 851-860
Vaughan OR, Davies KL, Ward JW, de Blasio MJ, Fowden AL, (2016), A physiological increase in maternal cortisol alters uteroplacental metabolism in pregnant ewes, J Physiol 594 6407-6418
Higgins JS, Vaughan OR, Fernandez de Liger E, Fowden AL, Sferruzzi-Perri AN, (2016), Placental phenotype and resource allocation to fetal growth are modified by the timing and degree of hypoxia during mouse pregnancy, J Physiol 594 1341-1356
De Blasio MJ, Boije M, Kempster SL, Smith GCS, Charnock-Jones DS, Denyer A, Hughes A, Wooding FBP, Blache D, Fowden AL, Forhead AJ, (2016), Leptin matures aspects of lung structure and function in the ovine fetus, Endocrinol, 157 395-404
Fowden AL, Forhead AJ, Sferruzzi-Perri AN, Burton GJ, Vaughan OR, (2015), Endocrine regulation of placental phenotype, Placenta, 36 Supplement 1, Trophoblast Research 29 S50-S59
Jellyman JK, Valenzuela OA, Fowden AL, (2015), Glucocorticoid programming of the hypothalamic-pituitary-adrenal axis and metabolic function: Animal studies from mouse to horse, J. Anim. Sci, 93 3245-3260
Vaughan OR, Fisher HM, Dionelis KN, Jeffreys ELC, Higgins JS, Musial B, Sferruzzi-Perri AN, Fowden AL, (2015), Corticosterone alters materno-fetal glucose partitioning and insulin signalling in pregnant mice, J. Physiol, 593 1307-1321
Sferruzzi-Perri AN, Vaughan OR, Haro M, Cooper WN, Musial B, Charalambous M, Pestana D, Ayyar S, Ferguson-Smith AC, Burton GJ, Constancia M, Fowden AL, (2013), An obesogenic diet during mouse pregnancy modifies maternal nutrient partitioning and the fetal growth trajectory, FASEB J, 27 3928-3937
Fowden AL, Forhead AJ, (2012), Insulin deficiency alters the metabolic and endocrine response to undernutrition in fetal sheep near term, Endocrinol, 153 4008-4018
Holdstock NB, Allen VL, Fowden AL, (2012), Pancreatic endocrine function in newborn pony foals after induced or spontaneous delivery at term, Equine Vet J, 44 Suppl 41, 30-37
Franko KL, Forhead AJ, Fowden AL, (2010), Differential effects of prenatal stress and glucocorticoid administration on postnatal growth and glucose metabolism in rats, J. Endo, 204 319-329
Coan PM, Angiolini E, Sandovici I, Burton GJ. Constancia M, Fowden AL, (2008), Adaptations in placental nutrient transfer capacity to meet fetal growth demands depend on placental size in mice, J. Physiol, 586 4567-4576
Forhead AJ, Curtis K, Kapstein E, Visser TJ, Fowden AL, (2006), Developmental control of iodothyronine deiodinases by cortisol in the ovine fetus and placenta near term, Endocrinol, 147 5988-5994
Constancia M, Angiolini E, Sandovici I, Smith P, Smith R, Kelsey G, Dean W, Ferguson-Smith A, Sibley C, Reik W, Fowden AL, (2005), Adaptation of nutrient supply to fetal demand in the mouse involves interaction between the Igf2 gene and placental transporter systems, PNAS, 102 19219-19224
Poore KR, Fowden AL, (2004), Insulin sensitivity in juvenile and adult pigs of low and high birth weight, Diabetologia, 47 340-348
Constancia M, Hemburger M, Hughes J, Dean W, Ferguson-Smith A, Fundele R, Stewart F, Kelsey G, Fowden A, Sibley C, Reik W, (2002), Placental-specific IGF2 is a major modulator of placental and fetal growth, Nature, 417 945-948
