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Abigail L Fowden

Professor of Perinatal Physiology
Tel: +44 (0)1223 333899, Fax: +44 (0)1223 333840, E-mail: alf1000@cam.ac.uk

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RESEARCH INTERESTS
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.  My research has three main themes:

(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 thatfetal 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

COLLEAGUES
Dr Owen Vaughan (Postdoctoral Research Associate)
Mr Orlando Valenzuela (PhD student)
Ms Josie Higgins (PhD student)
Ms Basia Musial (PhD student)
Ms Emma Eastwell (Research Technician)

COLLABORATORS in PDN
Dr Alison Forhead
Dr Amanda Sferruzzi-Perri
Dr Andrew Murray
Professor Graham Burton
Professor Dino Giussani

OTHER COLLABORATORS
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, Universiy of Cambridge.
Professor Wolf Reik, The Babraham Institute, Cambridge
Professor Colin Sibley, Dept. of Child Health, University of Manchester
Dr Juanita Jellyman, Dept of Obstetric & Gynecology, University of California, Los Angeles
Professor Anne Ferguson-Smith, Dept of Genetics, University of Cambridge

MAIN FUNDING
BBSRC
Horserace Betting Levy Board
MRC

SELECTED RECENT PUBLICATIONS (last 5 years – all publications here)

Reviews

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.

Vaughan, O.R., Sferruzzi-Perri A.N., Coan, P.M. & Fowden, A.L. (2012). Environmental regulation of placental phenotype: implications for fetal growth. Reprod. Fert. Develop. 24 80-96.

Fowden, A.L., Forhead, A.J. & Ousey, J.C. (2012). Endocrine adaptations in the foal during the perinatal period. Equine vet. J. 44  Suppl 41,130-139

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.

Fowden, A.L. & Moore, T. (2012). Maternal-fetal resource allocation: co-operation and conflict. Placenta 33 Suppl. 2 e11-e15.

Sferruzzi-Perri, A.N., Vaughan, O.R., Forhead, A.J. & Fowden, A.L. (2013). Hormonal and nutritional drivers of intrauterine growth. Curr. Opin. Clin. Nutr. Metab. Care 16 298-309.

Fowden, A.L., Jellyman, J.K., Valenzuela, O.A. & Forhead, A.J. (2013). Nutritional programming of intrauterine development: a concept applicable to the horse? J. Equine Vet. Sci. 33 295-304.

Original papers

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.

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.

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. 152 3202-3212.

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. 589 3659-3670.

Jellyman, J.K., Allen, V.L., Forhead, A.J., Holdstock, N.B. & Fowden, A.L. (2012). Hypothalamic-pituitary-adrenal axis function in pony foals after neonatal glucocorticoid overexposure. Equine Vet J. 44 Suppl 41, 38-42.

Vaughan, O.R., Sferruzzi-Perri, A.N. & Fowden, A.L. (2012). Maternal corticosterone regulates nutrient allocation to fetal growth in mice. J. Physiol. 590 5529-5540.

Jellyman, J.K., Martin-Gronet, M.S., Cripps, R.L., Giussani, D.A., Ozanne, S.E., Shen, Q.W., Du, M., Fowden, A.L. & Forhead, A.J. (2013). Effects of cortisol and dexamethasone on insulin signaling pathways in skeletal muscle of the ovine fetus during late gestation. PLoS One 7 e52363.

Jellyman, J.K., Allen, V.L., Holdstock, N.B. & Fowden, A.L. (2013). Glucocorticoid over-exposure in neonatal life alters pancreatic β cell function in newborn foals. J. Anim. Sci. 91 104-110.

Sferruzzi-Perri, A.N., Vaughan, O.R., Haro, M., Cooper, W.N., Musial, B., Charalambous, M., Pestana, D., Ayyar, S., Ferguson-Smith, A.C., Burton, G.J., Constancia M. & Fowden, A.L. (2013). An obesogenic diet during mouse pregnancy modifies maternal nutrient partitioning and the fetal growth trajectory. FASEB J 27 3928-3937.

Vaughan, O.R., Sferruzzi-Perri, A.N., Coan, P.M. & Fowden, A.L. (2013). Adaptations in placental phenotype depend on the route and timing of maternal dexamethasone administration in mice. Biol Reprod 89 80, 1-12.