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Birth, Distress and Disease



This volume examines the role of steroids and peptides in the regulation of pregnancy and preg-
nancy outcome, and their long-term effects including possible in¬‚uences on adult-onset dis-
eases. During pregnancy the placenta acts as a central regulator and coordinator of maternal and
fetal physiology, and of the onset of labor, through its production and regulation of steroids and
peptides. Perturbations to this regulatory system can result in poor pregnancy outcome, such as
preterm birth and low birth weight. These in turn are linked to diseases in later life. Intriguingly,
many of these regulatory actions of steroids and peptides also occur in the brain. The induction
and suppression of peptides by steroids appear to be the key to regulatory function in both brain
and placenta. These various interweaving strands, linking basic sciences with obstetrics, are all
reviewed in depth here producing a fascinating account of an important area of materno-fetal
medicine.
Birth, Distress and Disease
Placental“Brain Interactions



Edited by

Michael L. Power
Smithsonian National Zoological Park
Washington DC, USA
American College of Obstetricians and Gynecologists
Washington DC, USA

and


Jay Schulkin
American College of Obstetricians and Gynecologists
Washington DC, USA
Georgetown University School of Medicine
Washington DC, USA
National Institute of Mental Health
Bethesda MD, USA
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Published in the United States of America by Cambridge University Press, New York
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© Cambridge University Press 2005


This publication is in copyright. Subject to statutory exception and to the provision of
relevant collective licensing agreements, no reproduction of any part may take place
without the written permission of Cambridge University Press.

First published in print format 2005

isbn-13 978-0-511-12900-1 eBook (EBL)
isbn-10 0-511-12900-9 eBook (EBL)

isbn-13 978-0-521-83148-2 hardback
isbn-10 0-521-83148-2 hardback




Cambridge University Press has no responsibility for the persistence or accuracy of urls
for external or third-party internet websites referred to in this publication, and does not
guarantee that any content on such websites is, or will remain, accurate or appropriate.

Every effort has been made in preparing this publication to provide accurate and
up-to-date information that is in accord with accepted standards and practice at the time
of publication. Nevertheless, the authors, editors and publisher can make no warranties
that the information contained herein is totally free from error, not least because clinical
standards are constantly changing through research and regulation. The authors, editors
and publisher therefore disclaim all liability for direct or consequential damages
resulting from the use of material contained in this book. Readers are strongly advised
to pay careful attention to information provided by the manufacturer of any drugs or
equipment that they plan to use.
This volume is dedicated to the students and young (and not so
young) scientists we con¬dently predict will extend and improve on
the research presented here.
We would also like to acknowledge and thank certain individuals for
the personal contributions they have made to one of us (JS):
E. E. Krieckhaus; Ellen Oliver; and Stanley Schulkin.


Michael L. Power, Ph.D.
Jay Schulkin, Ph.D.
November 17, 2004
Contents




List of contributors page ix
Preface xi

Introduction: brain and placenta, birth and behavior, health and disease 1
Michael L. Power and Jay Schulkin


1 Placental expression of neurohormones and other neuroactive molecules
in human pregnancy 16
Felice Petraglia, Pasquale Florio and Wylie W. Vale


2 The regulation of human parturition 74
Roger Smith, Sam Mesiano, Richard Nicholson, Vicki Clifton, Tamas Zakar,
Eng-Cheng Chan, Andrew Bisits and Warwick Giles


3 Maternal nutrition and metabolic control of pregnancy 88
Michael L. Power and Suzette D. Tardif


4 Fetal HPA activation, preterm birth and postnatal programming 114
Deborah M. Sloboda, Timothy J. M. Moss, John P. Newnham and John R. G. Challis


5 Prenatal glucocorticoids and the programming of adult disease 142
Jonathan R. Seckl, Amanda J. Drake and Megan C. Holmes


6 Prenatal stress and stress physiology in¬‚uences human fetal and
infant development 183
Elysia Poggi Davis, Calvin J. Hobel, Curt A. Sandman, Laura Glynn, Pathik D. Wadhwa


7 Glucocorticoids and the ups and downs of neuropeptide gene expression 202
Alan G. Watts
viii Contents


8 Glucocorticoid facilitation of corticotropin-releasing hormone in the
placenta and the brain: functional impact on birth and behavior 235
Jay Schulkin, Louis Schmidt and Kristine Erickson


Index 269
List of contributors




Andrew Bisits Pasquale Florio
Mothers and Babies Research Centre, John Department of Pediatrics, Obstetrics and
Hunter Hospital, Newcastle, NSW, Australia Reproductive Medicine, University of Siena,
Siena School of Medicine, Siena, Italy
John R. G. Challis
Warwick Giles
Departments of Physiology, and Obstetrics
Mothers and Babies Research Centre,
and Gynaecology, University of Toronto,
John Hunter Hospital, Newcastle, NSW,
CIHR Group in Fetal and Neonatal Health
Australia
and Development, CIHR Institute of
Human Development, Child and Youth Laura Glynn
Health, Canada Department of Psychiatry and Human
Behavior, University of California, Irvine,
Eng-Cheng Chan
California, CA, USA
Mothers and Babies Research Centre, John
Hunter Hospital, Newcastle, NSW, Australia Calvin J. Hobel
Department of Obstetrics and Gynecology,
Vicki Clifton
Cedars Sinai Medical Center, Los Angeles,
Mothers and Babies Research Centre, John
California, CA, USA
Hunter Hospital, Newcastle, NSW, Australia
Megan C. Holmes
Elysia Poggi Davis Endocrinology Unit, University of
Department of Psychiatry and Human Edinburgh, Western General Hospital,
Behavior, University of California, Irvine, Edinburgh EH4 2XU, UK
California, CA, USA
Sam Mesiano
Amanda J. Drake Mothers and Babies Research Centre,
Endocrinology Unit, University of John Hunter Hospital, Newcastle, NSW,
Edinburgh, Western General Hospital, Australia
Edinburgh EH4 2XU, UK
Timothy J. M. Moss
Kristine Erickson School of Women™s and Infants™ Health
Molecular Neuroimaging Branch, National and the Women and Infants Research
Institute of Mental Health, Bethesda, MD, Foundation, University of Western Australia,
USA Western Australia
x List of contributors


John P. Newnham Jonathan R. Seckl
School of Women™s and Infants™ Health and Endocrinology Unit, University of
Edinburgh, Western General Hospital,
the Women and Infants Research
Edinburgh EH4 2XU, UK
Foundation, University of Western Australia,
Western Australia
Deborah M. Sloboda
Richard Nicholson School of Women™s and Infants™ Health and
Mothers and Babies Research Centre, John the Women and Infants Research
Hunter Hospital, Newcastle, NSW, Australia Foundation, University of Western Australia,
Western Australia
Felice Petraglia
Department of Pediatrics, Obstetrics and Roger Smith
Reproductive Medicine, University of Siena, Mothers and Babies Research Centre, John
Hunter Hospital, Newcastle, NSW, Australia
Siena School of Medicine, Siena, Italy

Suzette D. Tardif
Michael L. Power
Southwest National Primate Research
Department of Conservation Biology,
Nutrition Laboratory, Smithsonian™s National Center, San Antonio, TX, USA
Zoological Park, Washington DC, USA
Wylie W. Vale
Department of Research, American College
Peptide Biology Laboratory, Salk Institute,
of Obstetricians and Gynecologists,
La Jolla, California, CA, USA
Washington DC, USA
Pathik D. Wadhwa
Curt A. Sandman
Departments of Psychiatry and Human
Department of Psychiatry and Human
Behavior, and Obstetrics and Gynecology,
Behavior, University of California, Irvine,
University of California, Irvine, California,
California, CA, USA
CA, USA
Louis Schmidt
Alan G. Watts
Department of Psychology, McMaster
The NIBS-Neuroscience Program and
University, Canada
Department of Biological Sciences,
University of Southern California, Los
Jay Schulkin
Angeles, California, CA, USA
Department of Physiology and Biophysics,
Georgetown University School of Medicine; Tamas Zakar
Clinical Neuroendocrinology Branch, Mothers and Babies Research Centre, John
National Institute of Mental Health; and Hunter Hospital, Newcastle, NSW, Australia
Department of Research, American College
of Obstetricians and Gynecologists,
Washington DC, USA
Preface




In the summer of 2002, a small one-day conference was held at the of¬ces of the
American College of Obstetricians and Gynecologists in Washington DC. The pur-
pose of the conference was to consider the implications of the intriguingly con-
verging research areas of peptide regulation by steroids in both brain and placenta,
and how these research ¬ndings might enhance our understanding of the physio-
logical processes of human gestation and parturition. An important subtext of the
discussion was how events and processes at the beginning of life can affect health and
well-being decades later. Among the participants were both clinicians and basic
scientists; the research presented concerned both human studies and comparative
research on animal models; the perspectives examined ranged from clinical medicine
to evolutionary biology.
Our understanding of the physiological and regulatory processes that underlie
the timing and progression of labor and delivery remains incomplete. Perhaps the
most graphic indication of our inadequate understanding of this fundamental bio-
logical process is the current lack of accurate and effective clinical tools to either
predict or prevent preterm birth. In the USA, the rate of preterm birth continues
to rise, and half of preterm births are classi¬ed as idiopathic.
Progress is being made, however. A key paradigm shift is replacing the idea of the
placenta as a largely passive organ mainly responsible for delivering nutrients to

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