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

Miller, Adrian G.; Aplin, John D.; Westwood, Melissa

doi:10.1210/jc.2004-1052

Cited by 31 publications

(22 citation statements)

References 49 publications

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“…Placental explants in serum-free culture maintain the spatial and ontological relationships between cells and allow effective study of cytotrophoblast proliferation, differentiation, and apoptosis without the complications of multiple exogenous growth factors, binding proteins, and cytokines (32). Use of a mild enzymatic method to remove syncytiotrophoblast allowed direct access to the subjacent cytotrophoblast progenitor cell population (5, 6, 32).…”

Section: Discussionmentioning

confidence: 99%

“…Placental expression of the IGF1R is also reduced in pregnancies complicated by IUGR (25), and cytotrophoblast turnover is abnormal (44). A reduction in IGF levels is associated with IUGR (12,23,36), and experimental reduction in either IGF-I or -II results in decreased proliferation and survival of placental fibroblasts, whereas overexpression results in increased cell survival, proliferation, and migration (32). Exogenous IGF has been shown to increase placental growth in guinea pigs (41).…”

Section: Discussionmentioning

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

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163

132

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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: 99%

Section: Discussionmentioning

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

Self Cite

163

132

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show abstract

“…Recent work utilizing anti-sense adenoviral constructs for IGF-I and IGF-II demonstrate that they both enhance the proliferation and survival of placental fibroblast [19]; further indication of a survival role for IGFs in the placenta comes from the finding that IGF-I can also rescue both trophoblast and placental fibroblasts from apoptosis [19, 20]. …”

Section: The Igf Axis In the Placentamentioning

confidence: 99%

The IGF Axis and Placental Function

Forbes

Westwood²

2008

Horm Res Paediatr

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127

125

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It is well known that the insulin-like growth factor (IGF) axis is an important regulator of foetal growth and in recent years, it has been suggested that the ligands IGF-I and IGF-II may, in part, mediate this effect by promoting proper placental development and function. In other tissues, IGF effects on metabolism, proliferation and differentiation are primarily mediated via IGF binding protein-regulated interaction of IGFs with the type 1 IGF receptor and therefore here, we review the placental expression and postulated role, of each of the IGF axis components and discuss the cellular mechanisms through which these effects are exerted.

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“…IGFs influence autocrine and paracrine regulation of cell proliferation, migration, and survival. The placental IGF-IGFBP-receptor axis is a major influence on placental function and fetal growth [3].…”

Section: Introductionmentioning

confidence: 99%

The IGF Axis in Baboon Pregnancy: Placental and Systemic Responses to Feeding 70% Global Ad Libitum Diet

Li¹,

Levitz²,

Hubbard³

et al. 2007

Placenta

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Information on the influence of poor maternal nutrition on the regulation of responses to pregnancy, placental and fetal growth and development is critical to a better understanding of pregnancy physiology and pathophysiology. We determined normal changes and effects of controlled and monitored moderate nutrient restriction (NR) (global nutrient intake reduced to 70% of food consumed by mothers feeding ad libitum from 0.16 to 0.5 of gestation) in the baboon, on important hematological, biochemical, and hormonal indices of fetal growth and placental function. Serum IGF-I:IGFBP-3 ratio was lower in pregnant than control non-pregnant baboons feeding ad libitum. Serum concentrations of total and free IGF-I were decreased in NR mothers compared with controls (p < 0.05). The decrease in fetal IGF-I did not reach significance (p = 0.057). Serum IGF-I: IGFBP-3 ratio was decreased by NR in both mothers and fetuses. Maternal serum IGF-II was unchanged by NR. Placental IGF-I mRNA and protein abundance were similarly reduced whereas IGF-II mRNA increased in placental tissue of NR compared to control mothers. Systemic (maternal) and local (placental) IGFBP-1 and IGFBP-3 mRNA and protein abundance were unchanged by NR. Type 1 IGF receptor protein in the syncytiotrophoblast increased in NR. Type 2 IGF receptor protein was present in the stem villi core, and decreased after NR. We conclude that moderate NR in this important non-human primate model significantly disrupts the maternal and placental IGF-IGFBP axis and influences placental expression of this key system at the gene and protein level. Changes observed appear to be directed toward preserving placental growth.

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

Cited by 31 publications

References 49 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

The IGF Axis and Placental Function

The IGF Axis in Baboon Pregnancy: Placental and Systemic Responses to Feeding 70% Global Ad Libitum Diet

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