The Early Origins of Adult Health Research Group
An international leader in pregnancy and
fetal-development research, UniSA’s Early Origins of Adult Health Research
Group (EOAHRG) is involved in a variety of important projects looking at how
events before birth have an impact on health later in life.
The group uses a range of models and analytical techniques to investigate how the physiological environment before conception and during pregnancy can contribute to a range of conditions in adulthood such as obesity, diabetes, and cardiovascular disease.
Established as part of the Sansom Institute in 2005, the EOAHRG brings together many decades of collective experience in developmental physiology and is headed by UniSA’s Pro Vice Chancellor for Research and Innovation, Professor Caroline McMillen, and Dr Janna Morrison.
The group’s research can be classified into three broad areas: obesity and metabolic research, periconceptional and early embryo development, and oxygen sensing and cardiovascular development before birth.
Professor Caroline McMillen - laboratory co-head
Dr Janna Morrison – laboratory co-head
Dr Beverly Mühlhaüsler – senior researcher
Dr Sheridan Gentili – senior researcher
Research staff
Bernard Chuang – research assistant
Stacey Dunn – research assistant
Melissa Walker – research assistant
Postgraduate students
Petra Bos
Kimberley Botting
Jaime Duffield
Leewen Rattanatray
Andrew Snell
Olivia Wyss
Honours students
Christelle Ucinek
Shervie Lei
Heather Forbes
William Wang
Poh Seng Soo
The Early Origins of Adult Health Research Group enjoys productive relationships with a wide network of collaborators in Australia and around the world, including:
Australian collaborators
- Professor Michael Waters (Institute for Molecular Bioscience, University of Queensland)
- Dr Jim McFarlane (Department of Physiology, University of New England)
- Dr Ross Tellam (CSIRO Livestock Industries, Queensland)
- Dr Giuseppe Posterino (Discipline of Physiology, University of Adelaide)
- Dr Tony Vuocolo (CSIRO Livestock Industries, Queensland)
- Dr Cathie Coulter (Research Centre for the Early Origins of Adult Health, University of Adelaide)
- Dr Jeffrey Schwartz (Research Centre for the Early Origins of Adult Health, University of Adelaide)
- Dr Clare Roberts (Obstetrics and Gynaecology, University of Adelaide)
- Dr Simon Walker (South Australian Research and Development Institute)
International collaborators
- Dr Clare Adam (Rowett Research Institute, Aberdeen, UK)
- Professor Russ Anthony (University of Colorado, USA)
- Dr Sandy Davidge (Perinatal Research Centre, University of Edmonton, Canada)
- Professor Duane Keisler (Department of Animal Science, University of Missouri, USA)
- Professor David Olson (Perinatal Research Centre, University of Edmonton, Canada)
- Professor Charles Rosenfeld (Department of Paediatrics, South Western University, USA)
- Professor Dan Rurak (Research for Childrens and Womens Health, University of British Columbia, Canada)
- Professor Paul Sibbons (Bristol University, UK)
- Associate Professor Michael Symonds (School of Child Health, University of Nottingham, UK)
- Professor Kent Thornburg (Heart Research Centre, Oregon Health Sciences University, USA)
Below is a selection of current and recent research projects involving members of the Early Origins of Adult Health Research Group.
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Intrauterine growth restriction and development of the fetal cardiovascular system
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Epigenetic programming of the hypothalamo-pituitary-adrenal axis
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Differential expression of oxygen sensing genes lead to altered organ growth
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The early origins of obesity and diabetes: the role of maternal and fetal nutrition
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Expression of genes that regulate circadian rhythm in the heart
Intrauterine growth restriction and development of
the fetal cardiovascular system
Researchers: Caroline McMillen, Janna Morrison
Funding: NHMRC
Intrauterine growth restriction (IUGR) is associated
with an increased risk of cardiovascular disease in adulthood and
IUGR-affected infants have an increased risk of a number of conditions
resulting in longer hospital stays and increased mortality. This major
project is building upon previous EOAHRC research to test several hypotheses
surrounding the effects of placental restriction on regulation of fetal
blood pressure, including the role of the sympathetic nervous system and
endothelin.
The early origins of the metabolic syndrome
Researchers: Caroline McMillen, Beverly
Muhlhausler
Funding: NHMRC
More than half of all adults in Australia, the US and
the UK are either overweight or obese. Previous studies have established
that an increase in fetal nutrient supply may program childhood and adult
obesity, however the underlying mechanisms are not well understood. This
project aims to shed light on questions surrounding the early origins of
obesity, including determining whether an increase in maternal nutrition
results in an increased expression of the adipogenetic gene, Peroxisome
Proliferator-Activated Receptor γ, in fetal visceral adipose tissue.
Epigenetic programming of the
hypothalamo-pituitary-adrenal axis
Researchers: Caroline McMillen, Janna Morrison,
Catherine Suter
Funding: NHMRC
A range of stimuli including undernutrition and poor
postnatal maternal care act during critical windows of development to alter
the subsequent reactivity of the hypothalamo-pituitary-adrenal (HPA) axis to
stressors, resulting in poor cardiovascular and metabolic outcomes in
adulthood. This project brings together a team with expertise in embryology,
fetal physiology and epigenetics to investigate whether periconceptual
undernutrition and separately in vitro embryo culture result in programming
of the central or peripheral components of the fetal HPA axis.
Mechanisms involved in reduced cardiac contractility
as a consequence of growth restriction during fetal development
Researchers: Janna Morrison, Giuseppe Posterino
Funding: NHMRC
Intrauterine growth restriction (IUGR) is strongly
associated with a number of conditions in adulthood including an increased
risk of heart attack. This study aims to enhance understanding of the impact
of a poor intrauterine environment on heart development as well as
developing a better knowledge of normal developmental changes, ultimately
providing insight into the type of interventions required to improve the
health of low birth weight infants from birth to adulthood.
Differential expression of oxygen sensing genes lead
to altered organ growth
Researchers: Sheridan Gentili, Janna Morrison,
Caroline McMillen
Exposure to chronic fetal hypoxia results in the
sparing of growth of key organs such as the brain and adrenal and the
relative slowing of growth of other tissues including the fetal liver. The
mechanisms by which the fetus senses and responds to this low oxygen
environment is unclear. This study aims to determine whether tissues growth is regulated at the tissue level through the upregulation of an oxygen dependent sensing mechanisms, the Hypoxia Response
Factors, and through the alteration of local growth factor expression.
The early origins of obesity and diabetes: the role
of maternal and fetal nutrition
Researchers: Beverly Muhlhausler, Caroline McMillen
A growing number of studies have shown that individuals
who are exposed to either too much or too little nutrition before birth are
more likely to develop obesity and type 2 diabetes in later life. This
research is looking at how exposure of the mother, and hence her fetus, to
different levels of nutrition before birth can change the development of the
systems that regulate fat mass, appetite and insulin sensitivity before
birth and permanently affect their function in postnatal life.
Effects of periconceptional nutrition (in vivo and
ex vivo) on fetoplacental and postnatal development
Researchers: Caroline McMillen
A number of studies have demonstrated that the period
around the time of conception can have a major impact on fetoplacental
development. In particular, maternal undernutrition/overnutrition during the
periconceptional period or exposure of an embryo to in vitro culture can
lead to an alteration in cardiovascular, renal and placental function. In
addition, changes to the periconceptional environment during early embryo
development may ‘program’ the timing of birth. This project will investigate
how the environment of the developing embryo during the first seven days of
life causes changes in prenatal and postnatal growth, cardiovascular and
renal function and the development of adult diseases such as cardiovascular
disease and obesity.
Expression of genes that regulate circadian rhythm
in the heart
Researchers: Janna Morrison, David Kennaway
(University of Adelaide)
The seven per cent of babies born with low birth weight
in Australia have an increased risk of preterm delivery, neonatal death and
infant death, including sudden infant death. This dysregulation of
cardiorespiratory control may be due to altered development of the circadian
rhythm system. The mechanisms underlying this increased risk are not fully
understood but the development of the circadian rhythm in these babies may
be altered and thus play a role in their increased vulnerability. This
project is investigating the melatonin rhythm and the expression of clock
genes under normal development conditions and after fetal growth
restriction.
UniSA researchers are indicated in bold
Fletcher CJ, Roberts CT, Hartwich KM, Walker SK, McMillen IC (2007) ‘Somatic cell nuclear transfer in the sheep induces placental defects that likely precede fetal demise’ Reproduction In Press
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
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.
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.
Muhlhausler BS, Duffield JA, McMillen IC (2006) ‘Increased maternal nutrition stimulates Peroxisome Proliferator Activated Receptor-γ (PPAR-γ), adiponectin and leptin mRNA expression in adipose tissue before birth’. Endocrinology (electronic publication ahead of print) 2006-115
Farrand K, McMillen IC, Tanaka S, Schwartz J (2006) ‘Subpopulations of corticotrophs in the sheep pituitary during late’. Endocrinology 147:4762-4771
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 – Regulatory, Integrative and Comparative Physiology 29:R1399-R140
Muhlhausler BS, Duffield JA, McMillen IC (2006) ‘Increased maternal nutrition stimulates Peroxisome Proliferator Activated Receptor-γ (PPAR-γ), adiponectin and leptin mRNA expression in adipose tissue before birth’. Endocrinology (electronic publication ahead of print) 2006-115
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.
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 (electronic publication ahead of print) In Press.
De Blasio MJ, Gatford KL, McMillen IC, Robinson JS, Owens JA (2006) ‘Placental restriction of fetal growth increases insulin action, growth and adiposity in the young lamb’. Endocrinology (electronic publication ahead of print) 2006-0653.
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 13:516-522
T Spencer, KJ Botting, *JL Morrison and *GS Posterino\ (2006) ‘Contractile and Ca2+-handling properties of the right ventricular papillary muscle in the late gestation sheep fetus’. Journal of Applied Physiology 101(3) 728-33. *Co-senior authors. IF, 3.03; # of Cit, 0.
Morrison JL(2006) ‘Two-day subpressor cortisol infusion increases proliferation of cardiomyocytes in the late gestation sheep fetus’. Expert Reviews In Obstetrics and Gynecology, 1(2) 145-148.
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.
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.
Mühlhäusler 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.
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.
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 α-adrenergic blockade in fetal sheep during late gestation’. Journal of Physiology (London) 563:611-620.
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)
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.
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.
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.
McMillen IC and Robinson JS (2005) ‘Developmental Origins of the Metabolic Syndrome: Prediction, Plasticity and Programming’. Physiological Reviews 85:571-633.
Morrison JL, Rurak DW, Chien C, Kennaway DJ, Gruber N, McMillen IC and Riggs KW (2005) ‘Fetal circadian rhythm in melatonin, prolactin and behavioural state after maternal fluoxetine infusion’. Journal of the Society of Gynecologic Investigation, 12 356-364.
Morrison JL, Carmichael L, Homan J, White S, and Richardson BS (2005) ‘Cerebral blood flow during spontaneous and cholinergically induced behavioural states in the sheep fetus’. Pediatric Research 57 1-7. IF, 3.29; # of Cit, 0.
Morrison JL, KW Riggs, DW Rurak (2005) ‘Fluoxetine during pregnancy – impact on fetal development, reproduction, fertility and development’ 17 641-650. Featured paper. IF, 0.92; # of Cit, 1.
Schwartz J, Morrison JL (2005) Impact and mechanisms of physiological programming, American Journal of Physiology, 288(1) (2005) R11-15. IF, 3.41; # of Cit, 3.
The Early Origins of Adult Health Research Group is based in the Basil Hetzel Building at the University of South Australia’s City East campus in Adelaide.
For more information about the group and its activities, please contact us on:
Phone: +61 8 8302 2452
Fax: +61 8 8302 2389
Email:
sheridan.gentili@unisa.edu.au