Intrauterine growth restriction (IUGR) is associated with increased leptin synthesis and binding capability in neonates

Tzschoppe, Anja; Struwe, Ellen; Rascher, Wolfgang; Dörr, Helmuth G.; Schild, R. L.; Goecke, Tamme W.; Beckmann, Matthias W.; Hofner, Benjamin; Kratzsch, Jürgen; Dötsch, Jörg

doi:10.1111/j.1365-2265.2010.03943.x

Cited by 32 publications

(18 citation statements)

References 41 publications

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“…Written consent was collected from all subjects prior to the study. Placenta samples from a tissue collection of a previous study [24], [25], [26] were used for the analysis of CNN3 expression in intrauterine growth restriction (IUGR) and average for gestational age (AGA) placentas, containing 39 IUGR samples (gestational week 35.3 + 2.6 (SD)) and 31 AGA samples (gestational week 36.6 + 2.8 (SD)) as control.…”

Section: Methodsmentioning

confidence: 99%

CNN3 Regulates Trophoblast Invasion and Is Upregulated by Hypoxia in BeWo Cells

et al. 2014

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CNN3 is an ubiquitously expressed F-actin binding protein, shown to regulate trophoblast fusion and hence seems to play a role in the placentation process. In this study we demonstrate that CNN3 levels are upregulated under low oxygen conditions in the trophoblast cell line BeWo. Since hypoxia is discussed to be a pro-migratory stimulus for placental cells, we examined if CNN3 is involved in trophoblast invasion. Indeed, when performing a matrigel invasion assay we were able to show that CNN3 promotes BeWo cell invasion. Moreover, CNN3 activates the MAPKs ERK1/2 and p38 in trophoblast cells and interestingly, both kinases are involved in BeWo invasion. However, when we repeated the experiments under hypoxic conditions, CNN3 did neither promote cell invasion nor MAPK activation. These results indicate that CNN3 promotes invasive processes by the stimulation of ERK1/2 and/or p38 under normoxic conditions in BeWo cells, but seems to have different functions at low oxygen levels. We further speculated that CNN3 expression might be altered in human placentas derived from pregnancies complicated by IUGR and preeclampsia, since these placental disorders have been described to go along with impaired trophoblast invasion. Our studies show that, at least in our set of placenta samples, CNN3 expression is neither deregulated in IUGR nor in preeclampsia. In summary, we identified CNN3 as a new pro-invasive protein in trophoblast cells that is induced under low oxygen conditions.

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Section: Methodsmentioning

confidence: 99%

CNN3 Regulates Trophoblast Invasion and Is Upregulated by Hypoxia in BeWo Cells

et al. 2014

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“…SLR is generated either by alternative splicing or by shedding of the ectodomain of membrane-bound receptor isoforms [7]. Cord blood SLR has been shown to exert a negative effect on birth weight [8] and a recent study reports elevated SLR levels in the absence of a difference in leptin levels in intrauterine growth restriction compared to appropriate for gestational age newborns [9]. …”

Section: Introductionmentioning

confidence: 99%

Association of Cord Blood Leptin, Soluble Leptin Receptor, Insulin-Like Growth Factor-I and Insulin-Like Growth Factor-Binding Protein-1 on Birth Indices in Healthy Full-Term Newborns

Tennekoon

Poopalapillai²,

Karunanayake³

et al. 2014

Horm Res Paediatr

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Background: Leptin and insulin-like growth factor-I (IGF-I) promote fetal growth. Their availability is modulated by soluble leptin receptor (SLR) and insulin-like growth factor-binding proteins (IGFBP). Studies that accounted for SLR levels when investigating the association of leptin, IGF-I and IGFBPs on birth indices are scarce. Methods: Cord blood leptin, SLR, IGF-I, IGFBP-1 and their association with birth indices were studied in term newborns (n = 110; males = 60). Data were compared between males and females using the Mann-Whitney U test/unpaired Student's t test as appropriate. Univariate correlations and multiple regression analyses were performed to identify variables significantly influencing birth indices. Results: Birth indices were comparable between male and female newborns. Females had a significantly lower SLR (p = 0.0142), a higher leptin/Ponderal index (p = 0.033) and a higher free leptin index (leptin/SLR) (p = 0.0081). Leptin and male gender positively and IGFBP-1 negatively influenced birth weight (p = 0.0005, p = 0.02, and p = 0.005, respectively) and head circumference (p = 0.0052, p = 0.0098, and p = 0.0183, respectively) when accounted for other variables. When tested in a different multiple regression model, the free leptin index positively influenced crown-heel length (p = 0.0016) in addition to birth weight (p < 0.0001) and head circumference (p = 0.0016). Conclusions: In healthy full-term pregnancies, cord blood leptin and IGFBP-1 exert independent and opposing effects on fetal growth.

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“…Leptin has recently been proposed as a biomarker of fetal adiposity (24) and may provide a biological link for the fetal programming of later adult metabolic and cardiovascular health (10). The bioavailability of leptin is modulated by the soluble leptin receptor (sOB-R) (25), and the sOB-R has also been inversely linked to birth weight (26) and to intrauterine growth restriction (27). It has been proposed that the balance between leptin and sOB-R, or the free leptin index (FLI), might be a useful tool to assess leptin activity (28).…”

Section: Introductionmentioning

confidence: 99%

Adipokines in umbilical cord blood from children born large for gestational age

Lausten-Thomsen¹,

Christiansen

Hedley

et al. 2016

Journal of Pediatric Endocrinology and Metabolism

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Background: The etiology of childhood obesity and the associated morbidity is multifactorial. Recently, data suggesting a prenatal programming towards later childhood obesity and metabolic deregulation through the intrauterine environment has emerged. This study explored the concentrations of adipokines and their mutual relationship at birth in children born to non-diabetic mothers. Methods: Adiponectin, leptin and sOB-R were measured using ELISA-based commercial kits in umbilical cord blood from 60 neonates (30 born large for gestational age [LGA] and 30 born appropriate for gestational age [AGA]). Children exposed to maternal diabetes, chronic disease and preeclampsia were excluded. Results: The LGA group exhibited significantly elevated concentrations of leptin (p < 0.001) and of free leptin index (p < 0.001) and decreased sOB-R concentrations (p = 0.005) when compared to the AGA group, which persisted in multiple regression analysis after taking the gestational age into account (p = 0.048, p < 0.001 and p < 0.001, respectively). Only a trend towards a difference in adiponectin was demonstrated (p = 0.057) regardless of adjustment (p = 0.150). However, the leptin/adiponectin ratio was

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Intrauterine growth restriction (IUGR) is associated with increased leptin synthesis and binding capability in neonates

Abstract: Leptin-binding capability in venous cord blood is increased in IUGR newborns. Thus, via foetal programming, reduced biologically active leptin levels might contribute to a perturbed regulation of appetite.

Cited by 32 publications

References 41 publications

CNN3 Regulates Trophoblast Invasion and Is Upregulated by Hypoxia in BeWo Cells

CNN3 Regulates Trophoblast Invasion and Is Upregulated by Hypoxia in BeWo Cells

Association of Cord Blood Leptin, Soluble Leptin Receptor, Insulin-Like Growth Factor-I and Insulin-Like Growth Factor-Binding Protein-1 on Birth Indices in Healthy Full-Term Newborns

Adipokines in umbilical cord blood from children born large for gestational age

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