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This Article Full Text Full Text (PDF) All Versions of this Article: 295/1/E170    most recent 00047.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gatford, K. L. Articles by Sloboda, D. M. Search for Related Content PubMed PubMed Citation Articles by Gatford, K. L. Articles by Sloboda, D. M.

Repeated betamethasone treatment of pregnant sheep programs persistent reductions in circulating IGF-I and IGF-binding proteins in progeny

¹Research Centre for Early Origins of Adult Disease, Discipline of Obstetrics and Gynecology, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide; ²School of Women's and Infant's Health, The University of Western Australia, Perth; ³Women and Infants Research Foundation of Western Australia, Subiaco, Perth, Australia; and ⁴Canadian Institutes of Health Research Group in Fetal and Neonatal Health and Development, Departments of Physiology and Obstetrics and Gynecology, University of Toronto, Ontario, Canada

Submitted 24 January 2008 ; accepted in final form 15 May 2008

Exposure to synthetic glucocorticoids in utero markedly improves survival after preterm birth, but repeated exposures impair fetal and postnatal growth and are associated with evidence of insulin resistance in later life. The insulin-like growth factor (IGF) axis is an important regulator of growth and metabolism before and after birth. We have therefore investigated the effects of repeated maternal betamethasone injections on plasma IGF-I, IGF-II, and IGF-binding proteins (IGFBP) in fetal and postnatal progeny in the sheep. Pregnant sheep carrying male fetuses were injected with saline or betamethasone at 104, 111, and 118 days of gestation (dG, term 150 dG). Plasma samples were collected postmortem from fetuses before (75, 84, 101 dG) or after one (109 dG), two (116 dG), or three (121–122, 132–133, 145–147 dG) doses of saline or betamethasone and from progeny at 42 and 84 days of age. Fetal weight was reduced after two or more maternal betamethasone injections, and this effect persisted to term. Repeated betamethasone exposures reduced plasma IGF-I and total IGFBP in fetuses at 133 dG and progeny at 84 days, and reduced plasma IGFBP-3 at 84 days. Fetal plasma IGF-II tended to increase transiently at 109 dG following the first betamethasone injection. Fetal, placental, and/or postnatal weights correlated positively with concomitant plasma IGF-I, IGF-II, and total IGFBP. We conclude that repeated exposure to synthetic glucocorticoids in utero programs the IGF axis before and after birth, which may contribute to the adverse effects of betamethasone exposure on growth and metabolism.

antenatal glucocorticoids; pregnancy; programming; insulin-like growth factor-binding protein

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