Professor Caroline McMillen

Early Origins of Adult Health Research Group

1981 Bachelor of Medicine and Bachelor of Surgery, University of Cambridge, UK

1979 Doctor of Philosophy, University of Oxford, UK

1976 MA, University of Oxford, UK

1975 First Class Honours Degree in Physiological Sciences, University of Oxford, UK

• Professor McMillen is the Director of the Research Laboratory for the Early Origins of Adult Health and heads a research concentration of ~ 15 staff and students. Her laboratory has made significant and unique contributions in two major areas of developmental physiology. These are a definition of the fetal neuroendocrine and cardiovascular adaptations to intrauterine growth restriction and the impact of the periconceptional environment on fetal development.
• In a series of more than 20 publications, Professor McMillen’s laboratory has defined key fetal adaptive responses to a chronic restriction of placental substrate supply which may underpin the early programming of adult hypertension and obesity. This body of work represents a definition of the mechanistic basis of the physiological adaptations which are both critical for fetal survival and which initiate the reprogramming of endocrine and cardiovascular system development resulting in the association between fetal growth restriction and adverse cardiovascular and metabolic sequelae in adult life. The significance and importance of this work has been recognised through the award of an NHMRC Program Grant for ongoing work in this area.
• More recently, the laboratory has published a series of studies which highlight that alterations in the embryonic environment can reprogram the development of neuroendocrine and physiological systems into postnatal life. These studies have demonstrated that maternal undernutrition during the periconceptional period results in stimulation of the fetal pituitary-adrenal axis and reprograms the fetal cardiovascular system in late gestation and that the fetal ovine pituitary possesses a developmental plasticity that allows a remodelling of its corticotroph population. These studies represent a unique contribution to the literature on the potential epigenetic regulation of fetal development.
• Her work has featured in lead editorials in the Journal of Clinical Investigation and Endocrinology and she was recently invited to write a review on the Developmental Origins of Adult Disease by the Editorial Board of Physiological Reviews (Impact Factor 36.8).

Muhlhausler BS, Adam CL, Findlay JR, McMillen IC 2006 Increased maternal nutrition alters development of appetite regulatory network in the brain The FASEB Journal 20:E556-E565

McMillen IC, Edwards LJ, Duffield JA, Muhlhausler BS 2006 Regulation of leptin synthesis and secretion before birth: implication for the early programming of adult obesity. Reproduction 131:415-427

MacLaughlin SM, Muhlhausler BS, Gentili S, McMillen IC 2006 When in gestation do nutritional alterations exert their effects? A focus on the early origins of adult disease. Current Opinion in Endocrinology and Diabetes In Press

Hyatt M, Gopalakrishnan GS, Bispham J, Gentili S, McMillen IC, Rhind SM, Rae MT, Kyle CE, Brooks AN, Jones C, Budge H, Walker D, Stephenson T, Symonds ME 2006 Maternal nutrient restriction in early pregnancy programmes hepatic mRNA expression of growth hormone prolactin and insulin-like growth factor-II receptors hepatocyte growth factor Bax suppressor of cytokine signalling-3 and liver size in the adult male. Journal of Endocrinology In Press

Gentili S, Waters MJ, McMillen IC 2006 Differential regulation of Suppressor of Cytokine Signaling-3 (SOCS-3) in the liver and adipose tissue of the sheep fetus in late gestation. American Journal of Physiology 290:R1044-R1051

Gentili S, Schwartz J, Waters MJ, McMillen IC 2006 Prolactin and the expression of suppressor of cytokine signaling-3 (SOCS-3) in the sheep adrenal before birth. American Journal of Physiology ¡V Regulatory, Integrative and Comparative Physiology 291:R1399-R1405

Farrand K, McMillen IC, Tanaka S, Schwartz J 2006 Subpopulations of corticotrophs in the sheep pituitary during late Endocrinology 147:4762-4771

Muhlhausler BS, Duffield JA, McMillen IC 2006 Increased maternal nutrition stimulates Peroxisome Proliferator Activated Receptor-y (PPARy), adiponectin and leptin mRNA expression in adipose tissue before birth. Endocrinology:en.2006-1115

Lipsett J, Tamblyn M, Madigan K, Roberts P, Cool JC, Runciman SIC, McMillen IC, Robinson J, Owens JA 2006 Restricted fetal growth and lung development: A morphometric analysis of pulmonary structure. Pediatric Pulmonology 41:1138-1145

McMillen IC and Robinson JS (2005) Developmental Origins of the Metabolic Syndrome: Prediction, Plasticity and Programming. Physiological Reviews 85:571-633

Williams SJ, Hemmings DG, Mitchell JM, McMillen IC, Davidge ST (2005) Effects of maternal hypoxia or nutrient restriction during pregnancy on endothelial function in adult male rat offspring. Journal of Physiology (London) 565:125-135.

MacLaughlin SM, Walker SK, Roberts CT, Kleemann DO, McMillen IC (2005) Impact of periconceptional nutrition and fetal number on the relationship between maternal body weight changes in the periconceptional period and placental and fetal growth during early gestation. Journal of Physiology (London) 565: 111-124.

Morrison JL, Rurak DW, Chien C, Kennaway DJ, Gruber N, McMillen IC and Riggs KW (2005) Maternal fluoxetine infusion does not alter fetal endocrine and biophysical circadian rhythms in pregnant sheep. Journal of the Society for Gynecologic Investigation 12: 356-64.

McMillen IC, Duffield JA and Muhlhausler BS (2005) Prenatal Programming of Postnatal Obesity in Perinatal Programming: Early Life Determinants of Adult Health and Disease eds Hodgson and Coe (in press)

Danielson L, McMillen IC, Dyer JL and Morrison JL (2005) Restriction of placental growth results in greater hypotensive response to Ą-adrenergic blockade in fetal sheep during late gestation. Journal of Physiology (London) 563:611-620.

McMillen IC, Schwartz J, Coulter CL and Edwards LJ (2005) The early embryonic environment, the fetal pituitary-adrenal axis and the timing of parturition. Endocrine Res 30:845-50.

Danielson L, McMillen IC, Dyer JL and Morrison JL (2005) Restriction of placental growth results in greater hypotensive response to Ą-adrenergic blockade in fetal sheep during late gestation. Journal of Physiology (London) 563:611-620.

McMillen IC, Adam CL and Muhlhausler BS (2005) Topical Review: Early origins of obesity: Programming the appetite regulatory system. Journal of Physiology (London) 565:9-17.

Muhlhausler BS, Adam CL, Marrocco EM, Findlay PA, Roberts CT, McFarlane JR, Kauter KG and McMillen IC (2005) Impact of glucose infusion on the structural and functional characteristics of adipose tissue and on hypothalamic gene expression for appetite regulatory neuropeptides in the sheep fetus during late gestation. Journal of Physiology (London) 565: 185-195.

Muhlhausler BS, Adam CL, Marrocco EM, Findlay PA, Roberts CT, McFarlane JR, Kauter KG and McMillen IC (2005) Impact of glucose infusion on the structural and functional characteristics of adipose tissue and on hypothalamic gene expression for appetite regulatory neuropeptides in the sheep fetus during late gestation. Journal of Physiology (London) 565: 185-195.

Williams SJ, Campbell ME, McMillen IC and Davidge ST (2005) Differential effects of maternal hypoxia or nutrient restriction on carotid and femoral vascular function in neonatal rats. Am J Physiol Regul Integr Comp Physiol. 288:R360-3677.

Edwards LJ, McFarlane JR, Kauter KG and McMillen IC (2005) Impact of maternal undernutrition before and during pregnancy on maternal and fetal leptin and fetal adiposity in singleton and twin pregnancies. Am J Physiol Regul Integr Comp Physiol. 288:R39-45.

Mühlhäusler BS, McMillen IC, Rouzaud G, Findlay PA, Marrocco EM, Rhind SM and Adam CL (2004) Appetite regulatory neuropeptides are expressed in the sheep hypothalamus before birth. Journal of Neuroendocrinology 16: 502-507

Warnes KE, McMillen IC, Robinson JS and Coulter CL (2004) Metyrapone infusion stimulates adrenal growth without activating the cell cycle or the IGF system in the late gestation fetal sheep. Endocrine Research 30:535-539.

Warnes KE, McMillen IC, Robinson JS and Coulter CL (2004) Differential actions of metyrapone on the fetal pituitary-adrenal axis in the sheep fetus in late gestation. Biology of Reproduction 2004 Aug;71:620-628.

McMillen IC and Coulter CL (2004) The Feto-Placental Unit Encylopedia of Endocrinology and Endocrine Diseases Edited by Luciano Martini Elsevier Science San Diego CA

Gatford KL, De Blasio MJ, Thavaneswaran P, Robinson JS, McMillen IC and Owens JA (2004) Postnatal ontogeny of glucose homeostasis and insulin action in the sheep. American Journal of Physiology 86: E1050-1059.

Budge H, Edwards LJ, McMillen IC, Bryce A, Warnes KE, Stephenson T and Symonds ME (2004) Nutritional manipulation of fetal adipose tissue deposition and uncoupling protein 1 abundance in the fetal sheep; differential effects of timing and duration. Biology of Reproduction 71: 359-365

Yuen BSJ, Owens PC, Symonds ME, Keisler DH, McFarlane JR, Kauter KG and McMillen IC (2004) Effects of leptin on fetal plasma ACTH and cortisol concentrations and the timing of parturition in the sheep. Biology of Reproduction 70:1650-1657

Keating DJ, Rychkov GY, Adams, MB, Holgert H, McMillen IC and Roberts ML (2004) Opioid receptor stimulation suppresses the adrenal medulla hypoxic response in sheep by actions on Ca2+ and K+ channels. Journal of Physiology 555: 489-502.

M cMillen IC, Muhlhausler BS, Duffield JA and Yuen BSJ (2004) Prenatal programming of postnatal obesity: fetal nutrition and the regulation of leptin synthesis and secretion before birth. Proceedings of the Nutrition Society 63:405-412.

Morrison JLK, Riggs W, Chien C, Gruber N, McMillen IC and Rurak DW (2004) Chronic maternal fluoxetine infusion in pregnant sheep: effects on the maternal and fetal hypothalamic - pituitary-adrenal axes Pediatric Research 56:40-46

Williams SJ, Olson DM, Zaragoza D, Butler TG, Ross J, Coulter CL and McMillen IC (2004) Cortisol infusion decreases renin but not PGH, EP2 or EP4 mRNA expression in the kidney of the fetal sheep at d104-116. Pediatric Research 55: 637- 644.

Mühlhäusler BS, Roberts CT, Yuen BSJ, Budge H, Symonds ME, McFarlane JR, Kauter KG, Stagg P, Pearse JK and McMillen IC (2003) Determinants of fetal leptin synthesis, fat mass and circulating leptin concentrations in well nourished ewes in late pregnancy. Endocrinology 144: 4947-4954

Warnes KE, Coulter, CL, Robinson JS and McMillen IC (2003) The effect of infusion of metyrapone on arterial blood pressure and on the arterial blood pressure response to angiotensin II in the sheep fetus during late gestation. Journal of Physiology 552: 621-633

Coulter CL, Salkeld MD and McMillen IC (2003) Adrenal TGF ƒÒ1 mRNA levels fall during late gestation and are not regulated by cortisol in the sheep fetus. Molecular and Cellular Endocrinology 206: 85-91.

McMillen IC and Adams MB (2003) Adrenal Cortex: Role in Medullary Synthesis of PNMT Encylopedia of Hormones Volume 1 HL Henry and AW Norman (Editors-in-Chief) Academic Press Elsevier Science

McMillen IC, CL Coulter, JA Owens, JS Robinson and Edwards LJ (2003) Fetal neuroendocrine and cardiovascular adaptations to prenatal undernutrition: the fetal origins of adult disease? Havemeyer Foundation Monograph Series 8 Proceedings of a Workshop on Comparative Neonatology/Perinatology 67-69pp

Yuen BSJ, Owens PC, Muhlhausler BS, Roberts CT, Symonds ME, Keisler DH, McFarlane JR, Kauter KG, Evens Y and McMillen IC (2003) Leptin alters the structural and functional characteristics of adipose tissue before birth. The FASEB Journal 17: 1102-1104.

Coulter CL, Pestell RG, Ross JT, Salkeld MD, James S, Bennett HP and McMillen IC (2002) Effect of N-proopiomelanocortin (1-77) and (1-49) infusions on adrenal expression of cyclin D1 in the fetal sheep. Endocrine Research 28: 625-629.

Edwards LJ, Bryce AE, Coulter CL and McMillen IC (2002) Maternal undernutrition throughout pregnancy increases adrenocorticotrophin receptor and steroidogenic acute regulatory protein (StAR) gene expression in the adrenal gland of twin fetal sheep during late gestation. Molecular and Cellular Endocrinology 96:1-10.

Williams SJ, McMillen IC, Zaragoza D and Olson DM (2002) Placental restriction increases the expression of PGHS-2 and EP2 mRNA in the fetal sheep kidney during late gestation. Pediatric Research 52: 879-885.

Butler TG, Schwartz J and McMillen IC (2002) Differential effects of the early and late intrauterine environment on the development of corticotrophic cell types. Journal of Clinical Investigation 110: 783-791.

Yuen, BSJ, Owens PC, McFarlane JR, Symonds ME, Edwards LJ, Kauter KG and McMillen IC (2002) Circulating leptin concentrations in the sheep fetus are positively related to leptin mRNA expression in fetal adipose tissue and do not change in response to a decrease in maternal nutrition during late gestation. Biology of Reproduction 67: 911-916

Edwards LJ and McMillen IC (2002) Maternal undernutrition during the periconceptional period has long term effects on development of the fetal cardiovascular system in the sheep. American Journal of Physiology 283: R669-679

Edwards LJ, Peura T, Hartwich K, Rudiger S, McMillen IC and Walker S (2002) Postnatal growth and circulating ACTH and cortisol concentrations during the first month of life in cloned lambs. Endocrinology 143: 3699-3702

Coulter CL, McMillen IC, Bird IM and Salkeld MD (2002) Steroidogenic Acute Regulatory Protein (StAR) expression is decreased in the adrenal gland of the growth restricted sheep fetus during late gestation Biology of Reproduction 67: 584-590

Mühlhäusler BS, Roberts CT, McFarlane J, Kauter KG and McMillen IC (2002) Fetal leptin is a signal of fat mass independent of maternal nutrition in ewes fed at or above maintenance energy requirements. Biology of Reproduction 67: 493-499

Symonds ME, Budge H, Edwards LJ, Stephenson T and McMillen IC (2002) Maternal nutrition, cortisol and programming of fetal development. Perinatology 4: 67-74

Edwards LJ and McMillen IC (2002) Impact of maternal undernutrition during the periconceptional period, fetal number, and fetal sex on the development of the hypothalamo-pituitary adrenal axis in sheep during late gestation. Biology of Reproduction 66: 1562-1569.

Coulter CL, Ross JT, Owens JA , Bennett HPJ and McMillen IC (2002) Role of pituitary POMC-peptides and growth factors in the developmental biology of the adrenal gland. Archives in Physiology and Biochemistry 110:99-105.

Gatford KL, Clarke IJ, De Blasio MJ, McMillen IC, Robinson JS and Owens JA (2002) Perinatal growth and plasma GH profiles in adolescent and adult sheep. Journal of Endocrinology 173:151-159.

Buckley P, Rigda RS and McMillen IC (2002) Interaction between bed sharing and other sleep environments during the first six months of life. Early Human Development 66: 123-132

Professor Caroline McMillen has over 170 journal publications but only those published since 2002 are listed here.