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Effects of glucocorticoid treatment given in early or late gestation on growth and development in sheep

Published online by Cambridge University Press:  23 January 2013

S. Li ,
D. M. Sloboda ,
T. J. M. Moss ,
I. Nitsos ,
G. R. Polglase ,
D. A. Doherty ,
J. P. Newnham ,
J. R. G. Challis  and
T. Braun
S. Li*
Affiliation:
School of Women's and Infants’ Health, The University of Western Australia, Perth, Western Australia, Australia Women and Infants Research Foundation of Western Australia, Perth, Western Australia, Australia
D. M. Sloboda
Affiliation:
Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada
T. J. M. Moss
Affiliation:
School of Women's and Infants’ Health, The University of Western Australia, Perth, Western Australia, Australia The Ritchie Centre, Monash Institute of Medical Research and Department of Obstetrics and Gynaecology, Monash University, Victoria, Australia
I. Nitsos
Affiliation:
School of Women's and Infants’ Health, The University of Western Australia, Perth, Western Australia, Australia The Ritchie Centre, Monash Institute of Medical Research and Department of Obstetrics and Gynaecology, Monash University, Victoria, Australia
G. R. Polglase
Affiliation:
School of Women's and Infants’ Health, The University of Western Australia, Perth, Western Australia, Australia The Ritchie Centre, Monash Institute of Medical Research and Department of Obstetrics and Gynaecology, Monash University, Victoria, Australia
D. A. Doherty
Affiliation:
School of Women's and Infants’ Health, The University of Western Australia, Perth, Western Australia, Australia Women and Infants Research Foundation of Western Australia, Perth, Western Australia, Australia
J. P. Newnham
Affiliation:
School of Women's and Infants’ Health, The University of Western Australia, Perth, Western Australia, Australia Women and Infants Research Foundation of Western Australia, Perth, Western Australia, Australia
J. R. G. Challis
Affiliation:
School of Women's and Infants’ Health, The University of Western Australia, Perth, Western Australia, Australia Departments of Physiology and Obstetrics and Gynecology, University of Toronto, Toronto, Canada
T. Braun
Affiliation:
Department of Obstetrics, Charité University Berlin, Berlin, Germany
*
*Address for correspondence: Mr S. Li, School of Women's and Infants’ Health, The University of Western Australia, M550, Crawley, WA 6009, Australia. (Email [email protected])
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Abstract

Antenatal corticosteroids are used to augment fetal lung maturity in human pregnancy. Dexamethasone (DEX) is also used to treat congenital adrenal hyperplasia of the fetus in early pregnancy. We previously reported effects of synthetic corticosteroids given to sheep in early or late gestation on pregnancy length and fetal cortisol levels and glucocorticoids alter plasma insulin-like growth factor (IGF) and insulin-like growth factor binding protein (IGFBP) concentrations in late pregnancy and reduce fetal weight. The effects of administering DEX in early pregnancy on fetal organ weights and betamethasone (BET) given in late gestation on weights of fetal brain regions or organ development have not been reported. We hypothesized that BET or DEX administration at either stage of pregnancy would have deleterious effects on fetal development and associated hormones. In early pregnancy, DEX was administered as four injections at 12-hourly intervals over 48 h commencing at 40–42 days of gestation (dG). There was no consistent effect on fetal weight, or individual fetal organ weights, except in females at 7 months postnatal age. When BET was administered at 104, 111 and 118 dG, the previously reported reduction in total fetal weight was associated with significant reductions in weights of fetal brain, cerebellum, heart, kidney and liver. Fetal plasma insulin, leptin and triiodothyronine were also reduced at different times in fetal and postnatal life. We conclude that at the amounts given, the sheep fetus is sensitive to maternal administration of synthetic glucocorticoid in late gestation, with effects on growth and metabolic hormones that may persist into postnatal life.

Keywords

antenatal steroidsbetamethasonedexamethasonefetal brainIGF-insulin axis
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 4 , Issue 2 , April 2013 , pp. 146 - 156
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2013 

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