Maternal insulin-like growth factor-I infusion alters feto-placental carbohydrate and protein metabolism in pregnant sheep.

Liu, L; Harding, Jane E.; Evans, P C; Gluckman, Peter D.

doi:10.1210/endo.135.3.8070384

Cited by 61 publications

(22 citation statements)

References 40 publications

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“…This is supported by the findings that the UmBF in the EL group was higher than in EH and control groups, and this increased blood flow was sufficient to maintain foetal glucose uptake in EL foetuses, associated with normalisation of foetal growth rate after embolisation ceased. Maternal IGF-1 concentrations were also increased in the EL group, and this may also have contributed to a compensatory increase in utero-placental glucose uptake and hence foetal growth [32] . Furthermore, concentrations of many maternal amino acids were elevated in the EL group compared to both EH and control groups, a phenomenon commonly seen in human IUGR pregnancies [33] .…”

Section: Discussionmentioning

confidence: 92%

Taurine as a Marker for Foetal Wellbeing?

Boo¹,

Harding²

2006

Neonatology

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Background: After placental embolisation in pregnant sheep, we found elevated plasma taurine concentrations in several foetuses. These animals also had higher morbidity and mortality than foetuses with normal taurine concentrations. We therefore re-analysed our foetal growth and metabolism data with embolised animals divided into subgroups with high taurine concentrations (EH) and low taurine concentrations (EL). Objective: To investigate the hypothesis that foetal plasma taurine concentrations may be used as a marker for foetal wellbeing. Methods: Growth, metabolic and endocrine parameters were measured in normally grown foetal sheep and in those who had EH or EL after placental embolisation. Results: EH animals were more compromised than the EL animals, as shown by reductions in foetal weight and hind limb length and a failure to increase growth rate (chest girth increment) after embolisation. EH foetuses were hypoxaemic, hypoglycaemic and had increased lactate concentrations. Kidney, liver and adrenal weights were increased and thymus weight was decreased in EH animals. Maternal amino acid concentrations were elevated in EL animals. Foetal amino acid concentrations were more reduced in EH animals than in EL animals. Maternal IGF-1 concentrations were increased in EL, but not EH animals. Conclusions: Animals with EH were less able to compensate for the effects of embolisation than animals with EL. Taurine may have been released by the tissues as a protective mechanism against hypoxia-induced inflammation, or in an attempt to maintain osmotic balance. The connection between taurine and foetal wellbeing deserves further investigation.

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Section: Discussionmentioning

confidence: 92%

Taurine as a Marker for Foetal Wellbeing?

Boo¹,

Harding²

2006

Neonatology

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“…We have previously shown that short-term infusion of IGF-I into the maternal or fetal circulations alters placental metabolism, especially of lactate, suggesting that placental function can be influenced by maternal and fetal endocrine status (16,17). In those studies, maternal IGF-I infusions sufficient to increase maternal plasma IGF-I levels 3-fold for 3 h approximately doubled placental lactate production and fetal lactate uptake.…”

Section: Discussionmentioning

confidence: 93%

“…We have previously shown in pregnant sheep that shortterm infusion of IGF-I to the mother results in metabolic changes consistent with an increase in substrate uptake from mother to fetus (16), whereas IGF-I infusion to the fetus results in fetal anabolic changes (17). We have therefore speculated that prolonged elevation of IGF-I concentrations on both sides of the placenta would be expected to lead to enhanced fetal growth (16).…”

Section: F Etal Growth In Late Gestation Is Limited Largely Bymentioning

confidence: 99%

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Maternal Growth Hormone Treatment Increases Placental Diffusion Capacity But Not Fetal or Placental Growth in Sheep*

1997

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We tested the hypothesis that chronic maternal GH administration would increase fetal substrate supply, increase maternal and fetal insulin-like growth factor I (IGF-I) concentrations, and therefore enhance growth in the late gestation fetal sheep. Eleven ewes received bovine GH 0.1 mg/kg twice daily for 10 days, whereas 10 control ewes received saline. GH treatment increased placental capacity for simple diffusion (P Ͻ 0.01), with a trend toward an increase in placental capacity for facilitated diffusion (P ϭ 0.07). GH treatment also lowered maternal and fetal blood urea concentrations, and there was a trend toward increased fetal protein oxidation (P ϭ 0.07). Maternal but not fetal IGF-I and insulin concentrations increased. Fetal and placental growth were not altered by GH treatment. Maternal and fetal metabolic status was significantly affected by maternal food intake. We conclude that maternal GH treatment increases placental transport capacity, but that anabolic effects in the mother may limit fetal substrate supply and therefore prevent an increase in fetal growth. (Endocrinology 138: 5352-5358, 1997) F ETAL GROWTH in late gestation is limited largely by maternal substrate supply and mediated by a number of maternal and fetal hormones. Glucose is the major source of metabolic substrate for the late gestation fetus (1) and is supplied from the mother across the placenta. Birth size is proportional to cord blood insulin-like growth factor 1 (IGF-I) concentrations in a wide range of species (2), and gene deletion studies have shown clearly that fetal IGF-I is critical for fetal growth in late gestation (3-5).Birth size is also related to maternal GH and perhaps IGF-I concentrations (6 -8). GH and placental lactogen (PL) both induce relative insulin resistance in the mother, and thus are postulated to influence fetal growth by increasing maternal glucose levels and hence substrate supply available to the fetus (2). Nevertheless, previous studies of maternal GH administration have produced conflicting results regarding effects on fetal growth (9 -15).We have previously shown in pregnant sheep that shortterm infusion of IGF-I to the mother results in metabolic changes consistent with an increase in substrate uptake from mother to fetus (16), whereas IGF-I infusion to the fetus results in fetal anabolic changes (17). We have therefore speculated that prolonged elevation of IGF-I concentrations on both sides of the placenta would be expected to lead to enhanced fetal growth (16).We would therefore expect that conditions that both increased fetal glucose supply and increased maternal and fetal IGF-I concentrations would be most likely to enhance fetal growth. GH administration to the mother would be expected to increase maternal circulating blood glucose, fatty acid, and IGF-I concentrations. In the fetus, circulating IGF-I concentrations are regulated by fetal blood glucose and insulin concentrations (18 -20). Thus, maternal GH administration, by increasing maternal and hence fetal blood glucose concen...

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“…Insulin promotes lipogenesis within the maternal compartment, mediating glucose and amino acid uptake by the adipose and muscle tissue (Vernon et al, 1981;McNeill et al, 1997). IGF-I, in contrast, influences the placental transfer of glucose and amino acids (Kniss et al, 1994;Liu et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Effect of maternal body condition on placental and fetal growth and the insulin-like growth factor axis in Dorset ewes

Osgerby¹

2003

Reproduction

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This study investigated the effects of maternal body condition on fetal growth. Fetal and placental parameters from Dorset ewes of body condition score 2.0 (lean, n = 5), 3.5 (moderate, n = 7) and 5.0 (fat, n = 4) at mating were studied on day 65 of gestation. The fetal weight and fetal weight:crown-rump length ratio were greater in fat ewes than in ewes of moderate condition. The raised total and mean placentome weight in fat ewes compared with ewes of moderate condition may have contributed to their increased fetal growth. However, the fetal crown-rump length was not affected. With in situ hybridization, insulinlike growth factor II (IGF-II) mRNA and insulin-like growth factor binding protein 2 (IGFBP-2), -3 and -6 were all detected in the placentome capsule; IGF-II mRNA was also found in the mesoderm of the fetal villi and IGFBP-3 and IGFBP-6 were present in the caruncular stroma of the maternal villi. Ewes of moderate condition, which had the smallest placentae, had the greatest placental expression of IGF-II, IGFBP-2 and IGFBP-3. In the intercotyledonary endometrium, IGFBP-3, IGFBP-5 and uterine milk protein (UTMP) mRNA were all expressed in the glandular epithelium. IGFBP-3 and IGFBP-5 absorbance values were lowest in the lean ewes, whereas UTMP values were highest. Maternal insulin concentrations were greater in fat ewes, whereas plasma glucose and IGF-I concentrations in the fetal compartment were lowest in fat ewes. Therefore, in obese ewes, fetal and placental growth is increased in mid-gestation in association with higher maternal insulin concentrations and lower expression of IGFBPs in the maternal placentomes. Placental and fetal development in lean ewes may be promoted by reduced IGFBP expression in the placentomes and enhanced UTMP production by the endometrial glands. The ewes of moderate condition had the smallest fetuses and placentae coupled with the highest placental expression of IGF-II and IGFBPs.

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Maternal insulin-like growth factor-I infusion alters feto-placental carbohydrate and protein metabolism in pregnant sheep.

Cited by 61 publications

References 40 publications

Taurine as a Marker for Foetal Wellbeing?

Taurine as a Marker for Foetal Wellbeing?

Maternal Growth Hormone Treatment Increases Placental Diffusion Capacity But Not Fetal or Placental Growth in Sheep*

Effect of maternal body condition on placental and fetal growth and the insulin-like growth factor axis in Dorset ewes

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