The Early Origins of Adult Health Research Group
An
international leader in research in pregnancy and fetal development, UniSA's
Early Origins of Adult Health Research Group (EOAHRG) is engaged in important projects determining 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 from 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 for Health Research in 2005, the
EOAHRG brings together a research team with an international track record in
developmental physiology, epigenetics and endocrinology. The group's
research is focused in three broad areas: the early origins of obesity and
metabolic health, the periconceptional environment and the embryo, and
development of a healthy heart and cardiorespiratory system.
People
Dr Janna Morrison - Co-Head
Professor Caroline McMillen - Co-Head
Dr Larisa Bobrovskoya
Postdoctoral Fellows
Dr Song Zhang
Research staff
Stacey Dunn - Laboratory Coordinator
Bang Huang - Laboratory Officer
Darran Tosh - Laboratory Officer
Dr Kirsty Warnes - Laboratory Officer
Allison Martinez - Laboratory Officer
Postgraduate students
Kimberly Botting
Shervi Lei
Lisa Nicholas
Monalisa Padhee
Andrew Snell
Poh Seng Soo
Darran Tosh
Kimberly Wang
Honours students
Chin How Lim - Pharmacy 2011
Siew Mei Sim - Pharmacy 2011
Xin Yee Loke - Pharmacy 2011
Amreet Sing - Pharmacy 2011
Manjula Senthilkumaran - Bachelor of Medical and Pharmaceutical Sciences
2011
Erin McGillick - BSc in Laboratory Medicine 2010-11
Collaborators
The Early Origins of Adult Health Research Group works with a national
and international network of collaborators, including:
Australian collaborators
- Dr Jen Cropley (Victor Chang Research Institute, University of New South Wales)
- Dr Dave Kleemann (South Australian Research and Development Institute)
- Professor Manny Noakes (CSIRO Division of Human Nutrition)
- Dr Giuseppe Posterino (Discipline of Physiology, University of Adelaide)
- Dr Clare Roberts (Obstetrics and Gynaecology, University of Adelaide)
- Dr Catherine Suter (Victor Chang Research Institute, University of New South Wales)
- Dr Ross Tellam (CSIRO Livestock Industries, Queensland)
- Dr Tony Vuocolo (CSIRO Livestock Industries, Queensland)
- Dr Simon Walker (South Australian Research and Development Institute)
International collaborators
- Professor Philip Baker (Perinatal Research Centre, University of Edmonton, Canada)
- Associate Professor Helen Budge (School of Child Health, University of Nottingham, UK)
- Dr Sandy Davidge (Perinatal Research Centre, University of Edmonton, Canada)
- Professor Ron Magness (University of Madison-Wisconsin, US)
- Professor Jens Nyengaard (University of Asrhus)
- Professor David Olson (Perinatal Research Centre, University of Edmonton, Canada)
- Dr Sue Ozanne (Department of Clincial Biochemistry, University of Cambridge)
- 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 Michael Symonds (School of Child Health, University of Nottingham, UK)
- Professor Kent Thornburg (Heart Research Centre, Oregon Health Sciences University, USA)
Projects
Below is a selection of current and recent research projects involving members of the Early Origins of Adult Health Research Group.
Early Origins of a Life of Obesity
- Early origins of catch up growth and the metabolic syndrome
- Maternal obesity and the pathway to childhood obesity
- Pharmaceutical interventions in the battle against obesity
The Nutritional Environment of the Early Embryo and Health Outcomes in the Offspring
- The embryonic environment, epigenetics and the timing of birth
- Impact of in vitro culture of the embryo on metabolic and cardiovascular development
Development of a Healthy Heart and Cardiorespiratory System
- What is the role of the IGF signalling system in heart development?
- Blood pressure regulation and heart rate variability: role of fetal growth and hypoxia
- Effect of placental restriction on surfactant development in early gestation
- Role of undernutrition on surfactant development in late gestation in the sheep fetus
- Role of nutrient restriction versus hypoxia on surfactant development in the intrauterine growth restricted fetus of the guinea pig
- Expression of genes that regulate circadian rhythm in the male guinea pig
Early Origins of a Life of Obesity
Linking intrauterine growth restriction to proteins involved in metabolic syndrome in adult life
Researchers: Janna Morrison and Caroline McMillen
Being born small due to intrauterine growth restriction is associated with
accelerated growth in early postnatal growth and an increased risk of
developing metabolic disorders in adult life. We are investigating why small
babies are programmed to grow quickly after birth and determining changes in
key gene expression in muscle, fat and the liver which are important in the
early origins of poor metabolic health for the individual who was born
small.
Maternal obesity and the pathway to childhood obesity
Researchers: Caroline McMillen and Janna Morrison
Currently more than half of all adults in Australia, including women of
reproductive age, are either overweight or obese. Women who enter pregnancy
with a high Body Mass Index have an increased risk of delivering a large
baby with a high BMI and these babies in turn, have an increased risk of
becoming obese in early childhood and later adult life. Maternal obesity may
result in childhood obesity as a result of exposure of the early embryo, the
developing placenta and/or the fetus to maternal overnutrition. It is
important to understand the effects of maternal overnutrition on the embryo,
placenta and fetus as this will influence recommendations on the timing and
nature of nutritional interventions in pregnancy designed to limit the
impact of maternal obesity on the intergenerational cycle of obesity.
Pharmaceutical interventions in the battle against obesity
Researchers: Caroline McMillen and Janna Morrison
Understanding the mechanisms which link the risk of obesity to events before
birth will allow clinicians of the future to provide children who are born
to overweight, glucose-intolerant or diabetic mothers with a healthy start
to life. Evidence from many studies has shown that infants exposed to an
increased supply of nutrients before birth have an increased risk of being
overweight or obese as children and adults In normal adults, factors
released by fat cells play an important role in maintaining energy balance,
and changes in the levels of these factors in the fat cell or in the
circulation can lead to increased weight gain and poor sensitivity of the
body's tissues to the actions of hormones, such as insulin. Fat cells
develop before birth, and it has been shown that increases in nutrient
supply before birth can cause an early increase in fat deposition and may
change the functional properties of fat cells for life. This project is
investigating whether promoting an increase in fat deposition before birth
in the absence of any change in nutrient supply is associated with changes
in metabolic function before birth and an increased fat deposition and
dysregulation of the appetite-regulating neural network in the brain after
birth.
The Nutritional Environment of the Early Embryo and Health Outcomes in the Offspring
The Embryonic Environment, Epigenetics and the Timing of Birth
Researchers: Song Zhang, Caroline McMillen Janna Morrison
Preterm delivery remains a major health problem in western societies, with a
global incidence of 5 to 10% and whilst there are a series of known pathways
and risk factors which lead to preterm delivery, the mechanisms underlying
preterm delivery are largely unknown and poorly understood. The hypothalamo-pituitary-adrenal
(HPA) axis plays a critical role in fetal development, preparing the fetus
for the transition between the intra uterine environment and the outside
world. In long gestational species such as the human and the sheep the sress
axis is also involved in the hormonal cascade of events that signals the
timing of parturition. Our research group is currently determining how
changes in the nutritional environment of the early embryo lead to
epigenetic changes in the genes which determine the timing of birth and
which regulate the stress response in the offspring.
Impact of in vitro culture of the embryo on metabolic and cardiovascular development
Researchers: Song Zhang, Caroline McMillen and Janna Morrison
Changes in the nutritional environment of the early embryo e.g. culture of
the embryo as part of IVF programs can lead to changes in the development of
metabolic, endocrine and cardiovascular systems. We are investigating how
changes in the in vitro or in vivo environment of the developing embryo
results in changes in development before and after birth and the risk of
adult diseases such as cardiovascular disease and obesity.
Development of a Healthy Heart and Cardiorespiratory System
What is the role of the IGF signalling system in heart development?
Researchers: Janna Morrison and Doug Brooks
In Australia, intrauterine growth restriction occurs in 7% of babies. Large
studies show that these babies are at an increased risk of suffering from
heart disease in adult life. The mechanisms that link these events are not
clear. We have, shown that the IGF-1 receptor signalling pathway plays an
important role in heart growth in late gestation and this pathway is altered
in growth restricted fetuses. We hypothesize that up regulation of
components of the IGF-1 receptor signaling pathway result in changes in
heart development in growth restricted fetuses.
Blood pressure regulation and heart rate variability: role of fetal growth and hypoxia
Researchers: Janna Morrison and Caroline McMillen
Growth restricted fetuses have the same blood pressure as normally grown
fetuses but are at increased risk of hypertension in adult life. This
predisposition to hypertension is established in prenatal life when blood
pressure regulation is more reliant on the sympathetic and rennin
angiotensin systems. The role of hypoxia versus absolute growth restriction
is not fully understood. This project will compare blood pressure, blood
pressure regulation, heart rate and variability in heart rate in fetuses
that are normoxic or hypoxic, normally grown or growth restricted.
Effect of placental restriction on surfactant development in early gestation
Researchers: Sandra Orgeig and Janna Morrison (a collaboration with the
Molecular & Evolutionary Physiology of the Lung laboratory)
We have shown surfactant protein and gene expression are reduced in late
gestation in the growth restricted sheep fetus in a model of placental
restriction. We wish to establish the timeline for this altered
developmental trajectory, by investigating growth restricted fetuses during
early and mid-gestation, in relation to their plasma glucose and cortisol
concentration.
Role of undernutrition on surfactant development in late gestation in the sheep fetus
Researchers: Sandra Orgeig and Dr Janna Morrison (a collaboration with
the Molecular & Evolutionary Physiology of the Lung laboratory)
In the placental restriction model, the growth restricted fetus experiences
both nutrient and oxygen restriction (i.e. undernutrition and hypoxia). We
hypothesise that hypoxia has the dominant effect on surfactant maturation.
To determine the contribution of undernutrition alone, we will examine
surfactant maturation in mid to late gestation sheep fetuses exposed to
maternal undernutrition.
Role of nutrient restriction versus hypoxia on surfactant development in the intrauterine growth restricted fetus of the guinea pig
Researchers: Sandra Orgeig and Janna Morrison (a collaboration with the
Molecular & Evolutionary Physiology of the Lung laboratory)
Babies born preterm or born small for their gestational age are at an
increased risk of developing respiratory distress. We wish to establish the
mechanisms and timing of surfactant maturation during late gestation in
relation to environmental factors that lead to intrauterine growth
restriction.
Expression of genes that regulate circadian rhythm in the male guinea pig
Researchers: Janna Morrison and Dave Kennaway
In Australia, 7% of babies are born low birth weight. These babies are at 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. The melatonin rhythm and
the expression of clock genes in the guinea pig fetus under normal
development conditions and after fetal growth restriction will be
investigated.
Recent publications
UniSA researchers are indicated in bold.
Nyugen, Muhlhausler, Botting, Morrison, Maternal
undernutrition alters fat cell size distribution, but not lipogenic gene
expression, in the visceral fat of the late gestation guinea pig fetus,
Placenta, (2010 in press)
Rattanatray, MacLaughlin, Kleemann, Walker, Muhlhausler,
McMillen Impact of Maternal Periconceptional Overnutrition
on Fat Mass and Expression of Adipogenic and Lipogenic Genes in Visceral and
Subcutaneous Fat Depots in the Postnatal Lamb Endocrinology (2010 in press)
Zhang, Rattanatray, MacLaughlin, Cropley,
Suter, Molloy, Kleemann, Walker, Muhlhausler, Morrison and McMillen
Periconceptional Undernutrition in Normal and Overweight Ewes Leads to
Increased Adrenal Growth and Epigenetic Changes in Adrenal Igf2/H19 Gene in
Offspring. The FASEB Journal (2010 in press)
Orgeig S, Critterdon TA, Marchant C, McMillen IC
& Morrison JL, Intrauterine growth restriction delays
surfactant protein maturation in the sheep fetus, American Journal of
Physiology - Lung Cellular and Molecular Physiology, 298(4) (2010) L575-83.
BS Muhlhausler, JA Duffield, SE Ozanne, C Pilgrim, N Turner, JL
Morrison, IC McMillen, Insulin Signalling and the
Transition From Fetal Growth Restriction to Accelerated Postnatal Growth,
Journal of Physiology, 587(Pt 17) (2009): 4199-211.
BS Muhlhausler, JL Morrison and IC McMillen,
Rosiglitazone increases the expression of Peroxisome Proliferator-Activated
Receptor-γ target genes in adipose tissue, liver and skeletal muscle in the
sheep fetus in late gestation Endocrinology, 150(9) (2009) 4287-94.
J Dyer, IC McMillen, K Warnes, JL Morrison,
No Evidence for an Enhanced Role of Endothelial Nitric Oxide in the
Maintenance of Arterial Blood Pressure in the IUGR sheep fetus, Placenta,
30(8) (2009):705-10.
S Gentili, JL Morrison, IC
McMillen, Intrauterine growth restriction and differential patterns
of hepatic growth and expression of IGF-I, PEPCK and 11HSD-1 mRNA in the
sheep fetus in late gestation, Biology of Reproduction, 80(6) (2009) 1121-7.
SJ. Wallace, JL Morrison, KJ Botting and TW Kee, Second
harmonic generation and two-photon excited autofluorescence microscopy of
cardiomyocytes: quantification of cell volume and myosin filaments, Journal
of Biomedical Optics, 13(6) (2008) 064018-1 - 5.
JL Morrison, K.J. Botting, J.L. Dyer, S.J.
Williams, K.L. Thornburg, I.C. McMillen, Restriction of
placental function alters heart development in the sheep fetus, American
Journal of Physiology, 293(1) (2007) R306-13.
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.
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.
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.
Morrison JL, KW Riggs, DW Rurak (2005) 'Fluoxetine during pregnancy - impact
on fetal development, reproduction, fertility and development' 17 641-650.
Featured paper.
Schwartz J, Morrison JL (2005) Impact and mechanisms of physiological
programming, American Journal of Physiology, 288(1) (2005) R11-15.
Contact
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 2166 Fax:
+61 8 8302 2389 Email:
janna.morrison@unisa.edu.au