The IGF system during fetal-placental development of the mouse

Kleffens, Marjolein van; Groffen, Cora; Lindenbergh-Kortleve, Dicky J.; Neck, Johan W. van; González‐Parra, S.; Dits, Natasja F.; Zwarthoff, Ellen C.; Drop, Stenvert L. S.

doi:10.1016/s0303-7207(98)00041-0

Cited by 54 publications

(39 citation statements)

References 42 publications

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“…Previous reports indicate that IGFBP-5 may be associated with increased apoptosis. For example, IGFBP-5 co-localizes with areas of apoptosis in the interdigital zone of the developing mouse limb bud (van Kleffens et al, 1998); however, we now provide experimental evidence that IGFBP-5 can directly regulate apoptosis by interfering with IGF signalling in the mammary gland.…”

Section: Discussionmentioning

confidence: 67%

Insulin-like growth factor binding protein 5 and apoptosis in mammary epithelial cells

Marshman

Green

Flint

et al. 2003

Journal of Cell Science

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Insulin-like growth factors (IGFs) are important survival signals that can protect a range of cell types from apoptosis. Although IGF bioavailability is modulated by high affinity interactions with IGF-binding proteins (IGFBPs), there is currently no experimental evidence that IGFBPs regulate the survival function of IGFs in the mammary gland. We have examined IGFBP expression during mammary gland development and studied the effects of IGFBPs on IGF-mediated survival and signalling in mammary epithelial cells in culture. IGFBP-5 protein was greatly increased during days 1-3 of mammary gland involution, when levels of apoptosis are dramatically elevated to remodel the gland after lactation. Primary cultures of mammary epithelial cells (MECs) expressed IGFBP-5 from their basal surface suggesting that IGFBP-5 is suitably located to inhibit IGF signalling. Addition of exogenous IGFBP-5 and IGFBP-3 to MECs suppressed IGF-I-mediated survival, resulting in threefold greater apoptosis in cells incubated with IGF-I and IGFBP-5 compared with IGF-I alone. Examination of signalling pathways involved in apoptosis revealed that phosphorylation of PKB and the forkhead transcription factor, FKHRL1, was induced by IGFs, but that phosphorylation was blocked by IGFBP-5 and IGFBP-3. This study provides evidence that IGFBP-5 plays an important role in the regulation of apoptosis in the mammary gland

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Section: Discussionmentioning

confidence: 67%

Insulin-like growth factor binding protein 5 and apoptosis in mammary epithelial cells

Marshman

Green

Flint

et al. 2003

Journal of Cell Science

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“…The IGF are lowmolecular-weight polypeptides (7 kDa), with structural homology to proinsulin, which promote mitosis and differentiation. They play an important role in determining fetal and placental growth (van Kleffens et al 1998) Both maternal and fetal IGF-I levels affect fetal growth rate (Gluckman, 1995). IGF-I predominantly influences growth in late gestation and postnatally, whereas IGF-II has a stronger influence on embryonic growth in early development (Fig.…”

Section: The Insulin-like Growth Factor Axismentioning

confidence: 99%

“…The preimplantation embryo bathes in fluid that is rich in IGF and IGFBP (van Kleffens et al 1998). The IGF-II gene is expressed early after fertilisation and has been demonstrated in the two-cell-stage embryo (Heyner et al 1989).…”

Section: Nutrient Regulation Of Growthmentioning

confidence: 99%

“…Successful implantation, placental development and fetal growth depend on migration of the IGF-II-producing trophoblast into the maternal decidua (Minniti et al 1992). IGF-II is produced in abundance by the trophoblast cells of the placenta (van Kleffens et al 1998), and is particularly prevalent in sites of cell differentiation; its concentration is highest in the trophoblastic columns of anchoring villi, especially at the leading edge, implying it plays a pivotal role in trophoblastic invasion (Westwood, 1999). The maternal decidua and uterine vessels express IGFBP-1, which is involved in orchestrating trophoblast migration (Westwood, 1999).…”

Section: Nutrient Regulation Of Growthmentioning

confidence: 99%

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Nutrient insult in early pregnancy

2002

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Abbreviations: hCG, human chorionic gonadotrophin; IGF, insulin-like growth factor; IGFBP, insulin-like growth factor-binding protein; NVP, nausea and vomiting in pregnancy. Nutrient insults in early pregnancy, such as nutrient deprivation during famines, are often associated with an unfavourable outcome. Suboptimal nutrition in the early stage of gestation has been linked to a number of adverse effects on fetal growth and development. Historically, nausea and vomiting in pregnancy (NVP) was an important contributor to pregnancy-related mortality; indeed, Charlotte Bronte died from starvation and dehydration after suffering very severe NVP 4 months into her first pregnancy (Gaskell, 1858). Although NVP seldom now progresses to be life-threatening, it affects the majority of pregnant women, and potentially presents a challenge to nutrient intake in the most vulnerable period of development. Symptoms range from mild (nausea only) to severe (a level of vomiting that restricts nutrient intake and ultimately threatens metabolic and electrolyte balance). Although NVP has been documented for thousands of years, its cause has not yet been satisfactorily elucidated, but seems to be related to endocrinological changes. Pregnant women also frequently report dietary cravings and aversions during pregnancy which can be linked to both the incidence and severity of NVP. Paradoxically, NVP appears to be positively associated with a favourable outcome of pregnancy, including increased birth weight and gestational age. The mechanisms by which NVP favours the outcome of pregnancy are not known. They may be related to women increasing their nutrient intake to alleviate symptoms, improving the quality of their diet or reducing energy expenditure. Alternatively, adaptation to a reduced nutrient intake might stimulate the expression of growth factors and affect placentation or metabolism, thus favouring fetal growth when NVP resolves. Nausea and vomiting in pregnancy: Nutrient deprivation: Fetal development:Insulin-like growth factor: Maternal nutrition hCG, human chorionic gonadotrophin; IGF, insulin-like growth factor; IGFBP, insulin-like growth factor-binding protein; NVP, nausea and vomiting in pregnancy. Nausea and vomiting in pregnancyNausea and vomiting in pregnancy (NVP) affects 50-90 % of pregnant women (Broussard & Richter, 1998). It usually presents as one of the first signs of pregnancy, within 2-4 weeks of fertilisation, peaks at the end of the first trimester and resolves by week 20 (Anderson, 1994). NVP is usually experienced as a complication of the first trimester of pregnancy, but a small proportion of women experience symptoms throughout pregnancy (Broussard & Richter, 1998). Although the onset of symptoms occurs typically in the morning, thus generating the term 'morning sickness', many women are affected episodically throughout the day (Gadsby et al. 1993). Our retrospective study in Guildford (Al-Rasasi et al. 2001) shows that 72·6 % of pregnant women reported experiencing NVP, which is similar to the incidence...

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“…In pregnancy, PAPP-A is principally expressed in the syncytiotrophoblast of the placenta, which forms the main source of circulating maternal PAPP-A [4][5][6]. PAPP-A first identified in 1974, was later shown to be a protease that cleaves insulin-like growth factor binding protein -4 and -5 (IGFBP-4 and -5) to release free Insulin-like Growth Factors (IGF-1 and IGF-2) [7][8][9], and known to play a critical role in the regulation of fetal and placental growth [10][11][12]. Insulin-like Growth Factors (IGFs) are also thought to have an important role in the autocrine and paracrine control of trophoblast invasion of the decidua [13].…”

Section: Introductionmentioning

confidence: 99%

Association of low levels of first trimester Pregnancy Associated Plasma Protein (PAPP-A) with adverse pregnancy outcomes: An observational study

Ranganathan¹,

Fresen²,

Sarkar³

2017

Obstet Gynecol Rep

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Objectives: To explore the effects of low levels of first trimester Pregnancy Associated Plasma Protein-A (PAPP-A) on adverse pregnancy outcomes.Design: Single centre retrospective observational study. Setting: District general hospital.Population: Women with singleton pregnancies with low PAPP-A, attending Heatherwood and Wexham Park Hospital for first trimester combined screening for Down syndrome.Methods: Data was collected from Astraia Database and CMiS maternity system. Multiple linear regression models for birth weight and gestational age at delivery were developed after adjusting for confounding variables. Logistic regressions were dichotomised for preterm delivery into <34 weeks and ≥ 34 weeks, birth weight centiles, into <10 th centile and ≥10 th centile, and pre-eclampsia versus no pre-eclampsia. Main outcome measures:Preterm birth, small for gestational age (SGA) and pre-eclampsia.Results: PAPP-A levels of ≤0.4MoM is associated with SGA <10 th centile at p=0.04 with a positive predictive value (PPV) of 83.3% and negative predictive value (NPV) of 79.3%. Similarly, association with preterm birth <34 weeks is also significant at p=0.05 with PPV of 66% and NPV of 87.4%. A significant association with pre-eclampsia (p=0.6) could not be identified. In our study data of PAPP-A ≤0.4 MoM, for every 0.1MoM fall in PAPP-A, there was a reduction in birth weight by 78gm and an earlier birth by 5.3 days. Conclusion:There is an increased likelihood of preterm delivery and SGA with progressive reduction of PAPP-A levels below ≤0.4 MoM.

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The IGF system during fetal-placental development of the mouse

Cited by 54 publications

References 42 publications

Insulin-like growth factor binding protein 5 and apoptosis in mammary epithelial cells

Insulin-like growth factor binding protein 5 and apoptosis in mammary epithelial cells

Nutrient insult in early pregnancy

Association of low levels of first trimester Pregnancy Associated Plasma Protein (PAPP-A) with adverse pregnancy outcomes: An observational study

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