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

Kathryn Gatford, Julie Owens, Shaofu Li, Timothy Moss, John Newnham, John Challis, Deborah M Sloboda

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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 approximately 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.
Original languageEnglish
Pages (from-to)E170 - E178
Number of pages9
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume295
Issue number1
DOIs
Publication statusPublished - 2008
Externally publishedYes

Cite this

Gatford, Kathryn ; Owens, Julie ; Li, Shaofu ; Moss, Timothy ; Newnham, John ; Challis, John ; Sloboda, Deborah M. / Repeated betamethasone treatment of pregnant sheep programs persistent reductions in circulating IGF-I and IGF-binding proteins in progeny. In: American Journal of Physiology - Endocrinology and Metabolism. 2008 ; Vol. 295, No. 1. pp. E170 - E178.
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abstract = "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 approximately 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.",
author = "Kathryn Gatford and Julie Owens and Shaofu Li and Timothy Moss and John Newnham and John Challis and Sloboda, {Deborah M}",
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Repeated betamethasone treatment of pregnant sheep programs persistent reductions in circulating IGF-I and IGF-binding proteins in progeny. / Gatford, Kathryn; Owens, Julie; Li, Shaofu; Moss, Timothy; Newnham, John; Challis, John; Sloboda, Deborah M.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 295, No. 1, 2008, p. E170 - E178.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Repeated betamethasone treatment of pregnant sheep programs persistent reductions in circulating IGF-I and IGF-binding proteins in progeny

AU - Gatford, Kathryn

AU - Owens, Julie

AU - Li, Shaofu

AU - Moss, Timothy

AU - Newnham, John

AU - Challis, John

AU - Sloboda, Deborah M

PY - 2008

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N2 - 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 approximately 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.

AB - 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 approximately 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.

UR - http://ajpendo.physiology.org/content/295/1/E170.full.pdf+html

U2 - 10.1152/ajpendo.00047.2008

DO - 10.1152/ajpendo.00047.2008

M3 - Article

VL - 295

SP - E170 - E178

JO - American Journal of Physiology - Endocrinology and Metabolism

JF - American Journal of Physiology - Endocrinology and Metabolism

SN - 1522-1555

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