The Igf Axis at the Feto-Maternal Interface

Westwood, Melissa

doi:10.1017/s096227990100031x

Cited by 2 publications

(2 citation statements)

References 71 publications

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“…One-way analysis of variance with planned contrasts was used to assess significant (P Ͻ 0.05) differences between the groups: a significantly different from control (no treatment); b significantly different from IGF-I alone; c significantly different from IGF-II alone. and 150 -400 ng/ml, respectively) (13), and there are clinical data demonstrating a correlation between maternal IGF levels and birth weight (47). These observations suggest that maternal IGF can influence fetal growth.…”

Section: Discussionmentioning

confidence: 74%

“…Human fetal tissues including the placenta express IGF-I and IGF-II from early gestation. A partial deletion in the coding region of the human IGF-I gene results in severe intrauterine growth restriction (48), and IGF levels are correlated with birth weight (47). In mice, ablation of either the IGF-I or -II gene reduces birth weight to 60% that of normal littermates (7,29).…”

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confidence: 99%

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Insulin-like growth factor I and II regulate the life cycle of trophoblast in the developing human placenta

Forbes¹,

Westwood²,

Baker³

et al. 2008

American Journal of Physiology-Cell Physiology

162

131

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The main disorders of human pregnancy are rooted in defective placentation. Normal placental development depends on proliferation, differentiation, and fusion of cytotrophoblasts to form and maintain an overlying syncytiotrophoblast. There is indirect evidence that the insulin-like growth factors (IGFs), which are aberrant in pregnancy disorders, are involved in regulating trophoblast turnover, but the processes that control human placental growth are poorly understood. Using an explant model of human first-trimester placental villus in which the spatial and ontological relationships between cell populations are maintained, we demonstrate that cytotrophoblast proliferation is enhanced by IGF-I/IGF-II and that both factors can rescue cytotrophoblast from apoptosis. Baseline cytotrophoblast proliferation ceases in the absence of syncytiotrophoblast, although denuded cytotrophoblasts can proliferate when exposed to IGF and the rate of cytotrophoblast differentiation/fusion and, consequently, syncytial regeneration, increases. Use of signaling inhibitors suggests that IGFs mediate their effect on cytotrophoblast proliferation/syncytial formation through the MAPK pathway, whereas effects on survival are regulated by the phosphoinositide 3-kinase pathway. These results show that directional contact between cytotrophoblast and syncytium is important in regulating the relative amounts of the two cell populations. However, IGFs can exert an exogenous regulatory influence on placental growth/development, suggesting that manipulation of the placental IGF axis may offer a potential therapeutic route to the correction of inadequate placental growth.

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Section: Discussionmentioning

confidence: 74%

mentioning

confidence: 99%

Insulin-like growth factor I and II regulate the life cycle of trophoblast in the developing human placenta

Forbes¹,

Westwood²,

Baker³

et al. 2008

American Journal of Physiology-Cell Physiology

162

131

View full text Add to dashboard Cite

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Adenovirally Mediated Expression of Insulin-Like Growth Factors Enhances the Function of First Trimester Placental Fibroblasts

Miller

Aplin

Westwood³

2005

The Journal of Clinical Endocrinology & Metabolism

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IGFs are critical in fetal growth because of their role in placental development and function. In this study, we used adenovirus (Ad-IGF) to deliver sense or antisense IGF-I or IGF-II cDNA to human primary placental fibroblasts (PPF) in vitro to determine whether this could lead to enhanced placental cell function. PPFs virally transfected with Ad-IGF-I or Ad-IGF-II showed 7-fold (P < 0.01) and 3-fold (P < 0.01) increases in [(3)H]thymidine incorporation at 48 h post infection compared with nontransfected controls. In a coculture system designed to assess cell migration, nontransfected PPF cells positioned over a monolayer transfected by Ad-IGF-I or Ad-IGF-II showed a more than 10-fold (P < 0.01) and a 7-fold (P < 0.01) increase in migration compared with cells positioned above a nontransfected monolayer. After 96 h in culture, PPFs transfected with sense Ad-IGF-I or Ad-IGF-II showed 2% apoptosis compared with 16% of nontransfected cells, whereas 37% and 25% of cells transfected with antisense Ad-IGF-I or Ad-IGF-II were apoptotic. This work has established that cells of placental origin are amenable to adenoviral transfection and that IGFs exert autocrine and paracrine effects on proliferation, migration, and survival, suggesting that enhancement of IGF levels in the placenta may augment placental function and increase fetal growth.

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The Igf Axis at the Feto-Maternal Interface

Cited by 2 publications

References 71 publications

Insulin-like growth factor I and II regulate the life cycle of trophoblast in the developing human placenta

Insulin-like growth factor I and II regulate the life cycle of trophoblast in the developing human placenta

Adenovirally Mediated Expression of Insulin-Like Growth Factors Enhances the Function of First Trimester Placental Fibroblasts

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