Professor of Perinatal Physiology
Tel: +44 (0)1223 333899, Fax: +44 (0)1223 333840, E-mail: email@example.com
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 ultimate 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 the 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.
(Fig. Mechanisms of intrauterine programming From Fowden and Forhead (2009). Experimental Physiology 94 607-625)
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 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. Furthermore, we are examining the ontogeny and control of new peptides, such as leptin, which may influence maturation of the somatotrophic axis and have a role in early life programming of 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 adult metabolic consequences of the perinatal glucocorticoid over exposure.
Dr Juanita Jellyman (Research associate)
Mr Owen Vaughan (PhD student)
Mr Orlando Valenzuela (PhD student)
Ms Josie Higgins (PhD student)
Ms Basia Musial (PhD student)
COLLABORATORS in PDN
Professor Graham Burton
Professor Anne Ferguson-Smith
Dr Alison Forhead
Professor Dino Giussani
Dr Andrew Murray
Dr Amanda Sferruzzi-Perri
Professor Julie Owens, Dept of Obstetrics and Gynecology, University of Adelaide, Australia
Professor Gordon Smith, Dept of Obstetrics and Gynecology, University of Cambridge
Dr Miguel Constancia, Dept of Obstetrics and Gynecology, University of Cambridge
Dr Nicky Holdstock, Dept of Clinical Veterinary Medicine
Professor Wolf Reik, The Babraham Institute, Cambridge
Professor Colin Sibley, Dept of Child Health, University of Manchester
MAIN FUNDING: BBSRC, Horserace Betting Levy Board
SELECTED RECENT PUBLICATIONS (last 5 years)
Fowden, A.L., Ward, J.W., Wooding, F.P.B., Forhead, A.J. & Constancia, M. (2006). Programming placental nutrient transfer capacity J. Physiol. 572 5-15.
Fowden, A.L., Forhead, A.J. & Ousey, J.C. (2008). The endocrinology of equine parturition. Exp. Clin. Endocrinol.Diabetes 116 393-403.
Fowden, A.L., Forhead, A.J., Coan, P.M. & Burton, G.J. (2008). The placenta and intrauterine programming. J. Neuroendocrinol. 20 439-450.
Fowden, A.L. & Forhead, A.J. (2009). Hormones as epigenetic signals in developmental programming. Exp Physiol 94 607-625.
Fowden, A.L., Sferruzzi-Perri A.N., Coan, P.M., Constancia, M & Burton, G.J. (2009). Placental efficiency and adaptation: Endocrine regulation. J. Physiol. 587 3459-3472.
Fowden, A.L. & Forhead, A.J. (2009). Endocrine regulation of feto-placental growth. Hormone Research 72 257-265.
Fowden, A.L., Ward, J.W., Wooding, F.B.P. & Forhead, A.J. (2010). Developmental programming of the ruminant placenta. In Reproduction in Domestic Ruminants Editors: Lucy, M.C., Pate, J.L., Smith, M.F. & Spencer, T.E. pp 41-57. Nottingham University Press.
Vaughan, O.R. Forhead, A.J. & Fowden, A.L. (2011). Glucocorticoids and placental programming. In The Placenta and Human Developmental Programming Eds. Burton, G.J., Barker, D.J.P., Moffett, A., & Thornburg, K.L. pp 175-186. Cambridge University Press, Cambridge.
Fowden, A.L., Coan, P.M., Angiolini, E., Burton, G.J. & Constancia, M. (2011). Imprinted genes and the epigenetic regulation of placental phenotype. Prog Biophy Mol Biol 106 281-288.
Franko, K.L., Giussani, D.A., Forhead, A.J. & Fowden, A.L. (2007). Effects of dexamethasone on the glucogenic capacity of fetal, pregnant and non-pregnant adult sheep. J. Endo. 191 67-73.
Forhead, A.J., Jellyman, J.K., Gardner, D.S., Giussani, D.A., Kaptein E, Visser, T.J. & Fowden AL (2007). Differential effects of maternal dexamethasone treatment on circulating thyroid hormone concentrations and tissue deiodinase activity in the pregnant ewe and fetus. Endo. 148 800-805.
O’Connor, D.M., Blanche, D., Hoggard, N., Brookes, E., Wooding, F.B.P., Fowden, A.L. & Forhead, A.J. (2007). Developmental control of plasma leptin and adipose leptin mRNA in the ovine fetus during late gestation: role of glucocorticoids and thyroid hormones. Endo 148 3750-3757.
Fowden, A.L. & Forhead, A.J. (2007). Effects of pituitary hormone deficiency on the growth and glucose metabolism of the sheep fetus. Endo 148 4812-4820.
Owens, J.A., Gatford, K.L., De Blasio, M.J., Edwards, L.J., McMillen, I.C. & Fowden, A.L. (2007). Restriction of placental growth in sheep impairs insulin secretion but not sensitivity before birth. J. Physiol. 584 935-949.
Holmes, K., Charnock-Jones, S., Forhead, A.J., Giussani, D.A., Fowden, A.L., License, D., Kempster, S & Smith G.C.S. (2007). Localisation and control of expression of VEGF and VEGFR-2 receptor in fetal sheep intestine. Ped. Res. 63 143-148.
Forhead, A.J., Lamb, C.A., Franko, K.L., O’Connor, D.M., Wooding, F.B.P., Cripps, R.L., Ozanne, S.E., Blanche, D., Shen, QW, Du, M & Fowden, A.L. (2008). Role of leptin in the regulation of growth and carbohydrate metabolism in the ovine fetus during late gestation. J. Physiol 586 2393-2403.
Ousey, J.C., Fowden, A.L., Wilsher, S. & Allen, W.R. (2008). The effects of maternal health and body condition on the endocrine responses of neonatal foals. Equine Vet J 40 673-679.
Gatford, K.L., Mohammad, A., Harland, M.L., De Blasio, M.J., Fowden, A.L., Robinson, J.S. & Owens, J.A. (2008). Impaired beta cell function and inadequate compensatory increases in beta cell mass following restricted placental and fetal growth in sheep. Endo. 149 5118-5127.
Coan, P.M., Fowden, A.L., Constancia, M., Ferguson-Smith, A.C., Burton, G.J. & Sibley, C.P. (2008). Disproportionate effects of Igf2 gene knockout on placental morphology and diffusional exchange characteristics in the mouse. J. Physiol. 586 5023-5032.
Coan, P.M., Angiolini, E., Sandovici, I., Burton, G.J., Constancia, M. & Fowden, A.L. (2008). Adaptations in placental nutrient transfer capacity to meet fetal growth demands depend on placental size in mice. J. Physiol. 586 4567-4576.
Franko, K.L., Forhead, A.J. & Fowden, A.L. (2009). Effects of maternal dietary manipulation during different periods of pregnancy on hepatic glucogenic capacity of fetal and pregnant rats near term. Nutrition, Metabolism and Cardiovascular Diseases 19 555-562.
Forhead, A.J., Cutts, S., Matthews, P. & Fowden, A.L. (2009). Role of thyroid hormones in the developmental control of tissue glycogen in fetal sheep near term. Exp Physiol 94 1079-1087.
Coan, P.M., Vaughan, O.R., Sekita, Y., Finn, S.L., Burton, G.B., Constancia, M. & Fowden, A.L. (2010). Adaptations in placental phenotype support fetal growth during undernutrition of pregnant mice. J. Physiol 588 527-538.
Franko, K.L, Forhead, A.J. & Fowden, A.L. (2010). Differential effects of prenatal stress and glucocorticoid administration on postnatal growth and glucose metabolism in rats. J. Endo. 204 319-329.
Fowden, A.L. & Forhead, A.J. (2011). Adrenal glands are essential for activation of glucogenesis during undernutrition in fetal sheep near term. Am. J. Physiol. 300 E94-E102.
Forhead, A.J., Jellyman, J.K., Gilham, K., Ward, J.W., Blache, D & Fowden, A.L. (2011). Renal growth retardation following angiotensin II type 1 (AT1) receptor antagonism is associated with increased AT2 receptor protein in fetal sheep. J. Endo. 208 137-145.
Kempster, S.L., Belteki, G., Forhead, A.J., Fowden, A.L., Catalino, R.D., Lam, B.Y., Charnock-Jones, D.S. & Smith, G.C.S. (2011). Developmental control of the Nlrp6 inflammasome and a substrate, IL-18, in mammalian intestine. Am. J. Physiol. 300 G253-263.
Angiolini, E., Coan, P.M., Sandovici, I., Unuighe, O.H., Peck, G., Burton, G.J., Reik, W., Fowden, A.L. & Constancia, C. (2011). Developmental adaptations to increased fetal nutrient demand in mouse genetic models of Igf2-mediated overgrowth. FASEB J. 25 1737-1745.
Sferruzzi-Perri, A.N., Vaughan, O.R., Coan, P.M., Suciu, M.C., Darbyshire, R.,Constancia, M., Burton, G.J. & Fowden, A.L. (2011). Placental specific Igf2 deficiency alters developmental adaptations to undernutrition in mice. Endocrinol. (in press).
Holdstock, N.B., Allen, V.L. & Fowden, A.L. (2011). Pancreatic endocrine function in newborn pony foals after induced or spontaneous delivery at term. Equine Vet J. (in press).
Jellyman, J.K., Allen, V.L., Forhead, A.J., Holdstock, N.B. & Fowden, A.L. (2011). Hypothalamic-pituitary-adrenal axis function in pony foals after neonatal glucocorticoid overexposure. Equine Vet J. (in press).
Coan, P.M., Vaughan, O.R., McCarthy, J., Mactier, C., Burton, G.J., Constancia, M. & Fowden, A.L. (2011). Dietary composition programs placental phenotype in mice. J. Physiol. (in press).