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

S Li, Deborah M Sloboda, Timothy James Murugesan Moss, Ilias Nitsos, Graeme Polglase, Dorota A Doherty, John P Newnham, John R G Challis, Thorsten Braun

Research output: Contribution to journalArticleResearchpeer-review

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. ? Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2013.
Original languageEnglish
Pages (from-to)146 - 156
Number of pages11
JournalJournal of Developmental Origins of Health and Disease
Volume4
Issue number2
DOIs
Publication statusPublished - 2013

Cite this

Li, S ; Sloboda, Deborah M ; Moss, Timothy James Murugesan ; Nitsos, Ilias ; Polglase, Graeme ; Doherty, Dorota A ; Newnham, John P ; Challis, John R G ; Braun, Thorsten. / Effects of glucocorticoid treatment given in early or late gestation on growth and development in sheep. In: Journal of Developmental Origins of Health and Disease. 2013 ; Vol. 4, No. 2. pp. 146 - 156.
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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. ? Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2013.",
author = "S Li and Sloboda, {Deborah M} and Moss, {Timothy James Murugesan} and Ilias Nitsos and Graeme Polglase and Doherty, {Dorota A} and Newnham, {John P} and Challis, {John R G} and Thorsten Braun",
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Effects of glucocorticoid treatment given in early or late gestation on growth and development in sheep. / Li, S; Sloboda, Deborah M; Moss, Timothy James Murugesan; Nitsos, Ilias; Polglase, Graeme; Doherty, Dorota A; Newnham, John P; Challis, John R G; Braun, Thorsten.

In: Journal of Developmental Origins of Health and Disease, Vol. 4, No. 2, 2013, p. 146 - 156.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Effects of glucocorticoid treatment given in early or late gestation on growth and development in sheep

AU - Li, S

AU - Sloboda, Deborah M

AU - Moss, Timothy James Murugesan

AU - Nitsos, Ilias

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AU - Doherty, Dorota A

AU - Newnham, John P

AU - Challis, John R G

AU - Braun, Thorsten

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AB - 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. ? Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2013.

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