Fetal endocrine responses to chronic placental embolization in the late-gestation ovine fetus

Gagnon, Robert; Challis, John; Johnston, Laura; Fraher, L. J.

doi:10.1016/s0002-9378(94)70309-4

Cited by 93 publications

(65 citation statements)

References 23 publications

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“…During the period of placental insufficiency, alterations in fetal blood gas values were similar to those measured in previous studies in sheep using the UPE technique (11)(12)(13), and were similar to values measured by cordocentesis in human fetuses that were small for gestational age (15). We found that UPE altered the normal age-related increase in fetal arterial pressure.…”

Section: Discussionsupporting

confidence: 87%

“…In one study fetal MAP was not altered by 10 d of UPE starting at 122-125 d GA (13), while in another study fetal MAP was increased during 20 d of UPE between 110 and 130 d GA (11). The explanation for the apparent inconsistencies between studies is not clear, but it may be due to differences in the severity and gestational timing of UPE.…”

Section: Discussionmentioning

confidence: 95%

“…We have used the UPE technique as it is a controllable and reproducible means of restricting placental function that results in IUGR. Furthermore, many of its effects in the sheep have been documented (12)(13)(14) and resemble features of growth restricted human fetuses (15). We have measured plasma cortisol and renin as these hormones have been implicated in the regulation of blood pressure (16,17).…”

mentioning

confidence: 99%

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Placental Insufficiency and Fetal Growth Restriction Lead to Postnatal Hypotension and Altered Postnatal Growth in Sheep

et al. 2000

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Low birth weight has been associated with elevated arterial pressure in later life but mechanisms are unknown. Our aim was to determine the effects of low birth weight resulting from intrauterine growth restriction (IUGR) on fetal and postnatal arterial pressures and the potential roles of circulating cortisol and renin. We induced IUGR by umbilico-placental embolization (UPE) in fetal sheep from 120 d of gestation until birth (approximately 147 d); postnatal lambs (8 IUGR, 8 controls) were studied for 8 wk. Fetal and postnatal arterial pressures were measured and blood samples taken for measurement of gas tensions, cortisol concentrations and renin activity. In IUGR fetuses, mean arterial pressure (MAP) initially increased with UPE, but near term was not different to values in controls. IUGR lambs weighed 33% less than controls at birth and remained lighter than controls during the 8 postnatal weeks; their growth pattern was different to that of controls. IUGR lambs had lower MAP than controls, and this relative hypotension (Ϫ4 mm Hg) persisted throughout the 8 postnatal weeks. Covariate analysis showed that the relative hypotension of IUGR lambs could have resulted from their smaller size. Plasma cortisol concentrations were not different between IUGR and control animals before or after birth. Plasma renin activity was not different in postnatal IUGR lambs compared with controls. Thus, postnatal cortisol and renin levels were not consistent with the development of hypotension or hypertension. We conclude that late gestational IUGR in sheep leads to relative hypotension in the early postnatal period, probably a result of reduced body size. There is increasing evidence that low birth weight resulting from intrauterine growth restriction (IUGR) is associated with an increased risk of later illness. Associations have been demonstrated between low birth weight and an increased risk of adult-onset diseases such as hypertension, coronary heart disease and type II diabetes (1, 2). In adults, an inverse relationship has been found between arterial pressure and birth weight (3, 4) and this relationship has been found to be independent of current body size and lifestyle factors (1). Studies in children have also revealed inverse relationships between birth weight and arterial pressure (5). The relationship in adolescents is less clear with some studies finding inverse relationships between birth weight and arterial pressure (6) and others finding positive relationships (7). Based on epidemiologic findings, it has been proposed that hypertension is initiated in utero and is amplified with age (8).Several studies of fetal growth restriction in animals have also shown relationships between a sub-optimal intrauterine environment and arterial pressure. Mid-gestational uterine artery ligation in guinea pigs has been shown to produce growth restricted offspring with an elevated mean arterial pressure (9). In the rat, a low protein diet during pregnancy also leads to growth restricted offspring with an elevated systolic pressure...

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 99%

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Placental Insufficiency and Fetal Growth Restriction Lead to Postnatal Hypotension and Altered Postnatal Growth in Sheep

et al. 2000

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“…Circulating IGF-I concentrations fell acutely with embolisation, but had recovered in the saline-treated fetuses by the time of post mortem 10 days later (Bloomfield et al 2002a). Therefore, any changes in IGF-I or IGFBP mRNA levels associated with a growth-restricting insult, either mediated by increased circulating fetal cortisol concentrations secondary to embolisation (Gagnon et al 1994) or other mechanisms, may have resolved. Exogenous glucocorticoids have been reported to reduce both circulating IGF-I concentrations and tissue IGF-I mRNA levels (Luo & Murphy 1989, Jensen et al 2002.…”

Section: Discussionmentioning

confidence: 95%

Amniotic IGF-I supplementation of growth-restricted fetal sheep alters IGF-I and IGF receptor type 1 mRNA and protein levels in placental and fetal tissues

Shaikh

Bloomfield

Bauer³

et al. 2005

Journal of Endocrinology

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“…Elevated stress hormone levels could also have contributed. Placental embolisation leads to a marked increase in circulating cortisol and noradrenaline in late gestation sheep (Gagnon et al 1994). Cortisol has been shown to be a powerful stimulator of IGFBP-1 in humans independent of insulin and glucose (Conover et al 1993).…”

Section: Igf-i Concentrations In the Fetusmentioning

confidence: 99%

Chronic pulsatile infusion of growth hormone to growth-restricted fetal sheep increases circulating fetal insulin-like growth factor-I levels but not fetal growth

Bauer

Breier²,

Bloomfield³

et al. 2003

Journal of Endocrinology

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Intra-uterine growth restriction (IUGR) is a major cause of perinatal mortality and morbidity. Postnatally, growth hormone (GH) increases growth, increases circulating insulin-like growth factor (IGF)-I levels, and alters metabolism. Our aim was to determine if GH infusion to IUGR fetal sheep would alter fetal growth and metabolism, and thus provide a potential intra-uterine treatment for the IUGR fetus.We studied three groups of fetuses: control, IUGR+ vehicle and IUGR+GH (n=5 all groups). IUGR was induced by repeated embolisation of the placental vascular bed between 110 and 116 days of gestation (term=145 days). GH (3·5 mg/kg/day) or vehicle was infused in a pulsatile manner from 117 to 127 days of gestation.Embolisation reduced fetal growth rate by 25% (P<0·01) and reduced the weight of the fetal liver (20%), kidney (23%) and thymus (31%; all P<0·05). GH treatment further reduced the weight of the fetal kidneys (32%) and small intestine (35%; both P<0·04), but restored the relative weight of the fetal thymus and liver (P<0·05). Embolisation decreased fetal plasma IGF-I concentrations (48%, P<0·001) and increased IGF binding protein 1 (IGFBP-1) concentrations (737%, P<0·002). GH treatment restored fetal plasma IGF-I concentrations to control levels, while levels in IUGR+vehicle fetuses stayed low (P<0·05 vs control). IGFBP-1 and IGFBP-2 concentrations were about sevenfold lower in amniotic fluid than in fetal plasma, but amniotic and plasma concentrations were closely correlated (r=0·75, P<0·0001 and r=0·55 P<0·0001 respectively). Embolisation transiently decreased fetal blood oxygen content (40%, P<0·002), and increased blood lactate concentrations (213%, P<0·04). Both returned to pre-embolisation levels after embolisation stopped, but blood glucose concentrations declined steadily in IUGR+vehicle fetuses. GH treatment maintained fetal blood glucose concentrations at control levels.Our study shows that GH infusion to the IUGR fetal sheep restores fetal IGF-I levels but does not improve fetal growth, and further reduces the fetal kidney and intestine weights. Thus, fetal GH therapy does not seem a promising treatment stratagem for the IUGR fetus.

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Fetal endocrine responses to chronic placental embolization in the late-gestation ovine fetus

Cited by 93 publications

References 23 publications

Placental Insufficiency and Fetal Growth Restriction Lead to Postnatal Hypotension and Altered Postnatal Growth in Sheep

Placental Insufficiency and Fetal Growth Restriction Lead to Postnatal Hypotension and Altered Postnatal Growth in Sheep

Amniotic IGF-I supplementation of growth-restricted fetal sheep alters IGF-I and IGF receptor type 1 mRNA and protein levels in placental and fetal tissues

Chronic pulsatile infusion of growth hormone to growth-restricted fetal sheep increases circulating fetal insulin-like growth factor-I levels but not fetal growth

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