Postnatal effects of intrauterine treatment of the growth-restricted ovine fetus with intra-amniotic insulin-like growth factor-1.

Show simple item record Spiroski, AM en Oliver, Mark en Jaquiery, Anne en Prickett, TCR en Espiner, EA en Harding, Jane en Bloomfield, Francis en 2018-10-17T01:41:00Z en 2018-12 en
dc.identifier.issn 0022-3751 en
dc.identifier.uri en
dc.description.abstract KEY POINTS:Fetal growth restriction increases the risk of fetal and neonatal mortality and morbidity, and contributes to increased risk of chronic disease later in life. Intra-amniotic insulin-like growth factor-1 (IGF1) treatment of the growth-restricted ovine fetus improves fetal growth, but postnatal effects are unknown. Here we report that intra-amniotic IGF1 treatment of the growth-restricted ovine fetus alters size at birth and mechanisms of early postnatal growth in a sex-specific manner. We also show that maternal plasma C-type natriuretic peptide (CNP) products are related to fetal oxygenation and size at birth, and hence may be useful for non-invasive monitoring of fetal growth restriction. Intrauterine IGF1 treatment in late gestation is a potentially clinically relevant intervention that may ameliorate the postnatal complications of fetal growth restriction. ABSTRACT:Placental insufficiency-mediated fetal growth restriction (FGR) is associated with altered postnatal growth and metabolism, which are, in turn, associated with increased risk of adult disease. Intra-amniotic insulin-like growth factor-1 (IGF1) treatment of ovine FGR increases growth rate in late gestation, but the effects on postnatal growth and metabolism are unknown. We investigated the effects of intra-amniotic IGF1 administration to ovine fetuses with uteroplacental embolisation-induced FGR on phenotypical and physiological characteristics in the 2  weeks after birth. We measured early postnatal growth velocity, amino-terminal propeptide of C-type natriuretic peptide (NTproCNP), body composition, tissue-specific mRNA expression, and milk intake in singleton lambs treated weekly with 360 μg intra-amniotic IGF1 (FGRI; n = 13 females, 19 males) or saline (FGRS; n = 18 females, 12 males) during gestation, and in controls (CON; n = 15 females, 22 males). There was a strong positive correlation between maternal NTproCNP and fetal oxygenation, and size at birth in FGR lambs. FGR lambs were ∼20% lighter at birth and demonstrated accelerated postnatal growth velocity. IGF1 treatment did not alter perinatal mortality, partially abrogated the reduction in newborn size in females, but not males, and reduced accelerated growth in both sexes. IGF1-mediated upregulation of somatotrophic genes in males during the early postnatal period could suggest that treatment effects are associated with delayed axis maturation, whilst treatment outcomes in females may rely on the reprogramming of nutrient-dependent mechanisms of growth. These data suggest that the growth-restricted fetus is responsive to intra-amniotic intervention with IGF1, and that sex-specific somatotrophic effects persist in the early postnatal period. en
dc.format.medium Print-Electronic en
dc.language eng en
dc.relation.ispartofseries The Journal of physiology en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights This is the pre-peer reviewed version of the following article: Spiroski, A.M., Oliver, M.H., Jaquiery, A.L., Prickett, T.C.R., Espiner, E.A., Harding, J.E. & Bloomfield, F.H. Postnatal effects of intrauterine treatment of the growth-restricted ovine fetus with intra-amniotic insulin-like growth factor-1, The Journal of physiology 596(23): 5925-5945, which has been published in final form at This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. en
dc.rights.uri en
dc.subject Amniotic Fluid en
dc.subject Fetus en
dc.subject Animals en
dc.subject Animals, Newborn en
dc.subject Sheep en
dc.subject Fetal Growth Retardation en
dc.subject Natriuretic Peptide, C-Type en
dc.subject Insulin-Like Growth Factor I en
dc.subject Gene Expression Regulation, Developmental en
dc.subject Fetal Development en
dc.subject Pregnancy en
dc.subject Female en
dc.subject Male en
dc.title Postnatal effects of intrauterine treatment of the growth-restricted ovine fetus with intra-amniotic insulin-like growth factor-1. en
dc.type Journal Article en
dc.identifier.doi 10.1113/jp274999 en
pubs.issue 23 en
pubs.begin-page 5925 en
pubs.volume 596 en
dc.rights.holder Copyright: The authors, The Physiological Society en
dc.identifier.pmid 29235113 en
pubs.end-page 5945 en
pubs.publication-status Published en
dc.rights.accessrights en
pubs.subtype Research Support, Non-U.S. Gov't en
pubs.subtype Journal Article en
pubs.elements-id 719435 en Liggins Institute en LiFePATH en
dc.identifier.eissn 1469-7793 en
pubs.record-created-at-source-date 2017-12-14 en
pubs.dimensions-id 29235113 en

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