The adipokine preadipocyte factor-1 is downregulated in preeclampsia and expressed in placenta

Schrey, S; Wurst, Ulrike; Ebert, Thomas; Kralisch, Susan; Drewlo, Sascha; Stepan, Holger; Lössner, Ulrike; Platz, Martin; Kratzsch, Jürgen; Stümvoll, Michael; Faßhauer, Mathias

doi:10.1016/j.cyto.2015.07.021

Cited by 13 publications

(11 citation statements)

References 32 publications

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“…syncytiotrophoblast, a placental progenitor [22]. The latter however diasagrees with a previous study showing absence of DLK1 in all the epithelial trophoblasts [19].…”

Section: Another Recent Study Reports Expression Of Dlk1 In Placentalsupporting

confidence: 83%

“…In agreement, increased placental expression of DLK1 is associated with increased birth weight [23]. On the other hand, low maternal levels of circulating DLK1 have been associated with pregnancy complications [22]. Unrestricted somatic stem cells in the umbilical cord blood express DLK1 mRNA whereas low or no expression resided within the mesenchymal stromal cell population of the same compartment [24].…”

Section: Another Recent Study Reports Expression Of Dlk1 In Placentalmentioning

confidence: 86%

“…Finally, in the placenta, DLK1 is reported in endothelial cells and trophoblasts in man [22] and mouse [52,59,62] although trophoblasts were previously reported negative in humans [19]. Maternal serum levels of DLK1 are increased during pregnancy in both mouse [50] and human [19,22] and it is the fetus, not the placenta, which is the source of circulating maternal DLK1 [63]. Due to DLK1's high renal clearance, maternal circulating DLK1 most likely originates from the fetal urine [64].…”

Section: Dlk1 Gene Expression Is Conserved In Mousementioning

confidence: 99%

“…In the extra embryonic tissue published data shows that DLK1 is present as early as GA 5 and remains there until birth [19][20][21][22] (Table 1). During this period DLK1 is found within the endodermal cells of the yolk sack [19] and mesenchymal fibroblasts in the placenta [20].…”

Section: Extra Embryonic Tissuesmentioning

confidence: 99%

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The imprinted gene Delta like non-canonical Notch ligand 1 (Dlk1) is conserved in mammals, and serves a growth modulatory role during tissue development and regeneration through Notch dependent and independent mechanisms

Traustadóttir

Lagoni

Ankerstjerne

et al. 2019

Cytokine & Growth Factor Reviews

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“…syncytiotrophoblast, a placental progenitor [22]. The latter however diasagrees with a previous study showing absence of DLK1 in all the epithelial trophoblasts [19].…”

Section: Another Recent Study Reports Expression Of Dlk1 In Placentalsupporting

confidence: 83%

Section: Another Recent Study Reports Expression Of Dlk1 In Placentalmentioning

confidence: 86%

Section: Dlk1 Gene Expression Is Conserved In Mousementioning

confidence: 99%

Section: Extra Embryonic Tissuesmentioning

confidence: 99%

See 2 more Smart Citations

The imprinted gene Delta like non-canonical Notch ligand 1 (Dlk1) is conserved in mammals, and serves a growth modulatory role during tissue development and regeneration through Notch dependent and independent mechanisms

Traustadóttir

Lagoni

Ankerstjerne

et al. 2019

Cytokine & Growth Factor Reviews

View full text Add to dashboard Cite

show abstract

“…The potential clinical significance of clinical measurement of DLK1 is underlined by the fact that we have previously reported that these two measures were the most effective predictors of neonatal morbidity in pregnancies where the baby was suspected to be small on the basis of ultrasonic fetal biometry[26]. Previous studies have reported contradictory associations between cord blood DLK1 levels and birth weight [28], as well as in complications of pregnancy[29]. Those studies used a commercial ELISA which reports DLK1 levels that were ˜100x lower than values reported in both the original pioneering work on DLK1 as a soluble factor in pregnancy[7] and the values measured in this study.…”

Section: Discussionmentioning

confidence: 99%

Fetus-derived DLK1 is required for maternal metabolic adaptations to pregnancy and is associated with fetal growth restriction

et al. 2016

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Pregnancy is a state of high metabolic demand. Fasting diverts metabolism to fatty acid oxidation, and the fasted response occurs much more rapidly in pregnant women than in the non-pregnant state. The product of the imprinted Delta-like homologue 1 gene (DLK1) is an endocrine signaling molecule that reaches a high concentration in the maternal circulation during late pregnancy. By utilising murine models with deleted Dlk1 we show that the fetus is the source of maternal circulating DLK1. In the absence of fetally-derived DLK1, the maternal fasting response is impaired. Furthermore, we found that maternal circulating DLK1 levels predict embryonic mass in mice and can differentiate healthy small for gestational age (SGA) from pathologically small infants in a human cohort. Therefore measurement of DLK1 in maternal blood may be a valuable method for diagnosing human disorders associated with impaired DLK1 expression, and to predict poor intrauterine growth and complications of pregnancy.

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Trophoblast Side-Population Markers are Dysregulated in Preeclampsia and Fetal Growth Restriction

Wong,

Hartmann,

Simmons

et al. 2024

Stem Cell Rev and Rep

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Dysregulated progenitor cell populations may contribute to poor placental development and placental insufficiency pathogenesis. Side-population cells possess progenitor properties. Recent human trophoblast side-population isolation identified enrichment of 8 specific genes (CXCL8, ELL2, GATA6, HK2, HLA-DPB1, INTS6, SERPINE3 and UPP1) (Gamage et al. 2020, Stem Cell Rev Rep). We characterised these trophoblast side-population markers in human placenta and in placental insufficiency disorders: preeclampsia and fetal growth restriction (FGR). Trophoblast side-population markers localised to mononuclear trophoblasts lining the placental villous basement membrane in preterm control, preeclamptic and FGR placental sections (n = 3, panel of 3 markers/serial section). Analysis of single-cell transcriptomics of an organoid human trophoblast stem cell (hTSC) to extravillous trophoblast (EVT) differentiation model (Shannon et al. 2022, Development) identified that all side-population genes were enriched in mononuclear trophoblast and trophoblasts committed to differentiation under hTSC culture conditions. In vitro validation via 96 h time course hTSC differentiation to EVTs or syncytiotrophoblasts (n = 5) demonstrated ELL2 and HK2 increased with differentiation (p < 0.0024, p < 0.0039 respectively). CXCL8 and HLA-DPB1 were downregulated (p < 0.030, p < 0.011 respectively). GATA6 and INTS6 increased with EVT differentiation only, and UPP1 reduced with syncytialisation. SERPINE3 was undetectable. Trophoblast side-population marker mRNA was measured in human placentas (< 34-weeks’ gestation; n = 78 preeclampsia, n = 30 FGR, and n = 18 gestation-matched controls). ELL2, HK2 and CXCL8 were elevated in preeclamptic (p = 0.0006, p < 0.0001, p = 0.0335 respectively) and FGR placentas (p = 0.0065, p < 0.0001, p = 0.0001 respectively) versus controls. Placental GATA6 was reduced in pregnancies with preeclampsia and FGR (p = 0.0014, p = 0.0146 respectively). Placental INTS6 was reduced with FGR only (p < 0.0001). This study identified the localisation of a unique trophoblast subset enriched for side-population markers. Aberrant expression of some side-population markers may indicate disruptions to unique trophoblast subtypes in placental insufficiency. Graphical Abstract

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The adipokine preadipocyte factor-1 is downregulated in preeclampsia and expressed in placenta

Cited by 13 publications

References 32 publications

The imprinted gene Delta like non-canonical Notch ligand 1 (Dlk1) is conserved in mammals, and serves a growth modulatory role during tissue development and regeneration through Notch dependent and independent mechanisms

The imprinted gene Delta like non-canonical Notch ligand 1 (Dlk1) is conserved in mammals, and serves a growth modulatory role during tissue development and regeneration through Notch dependent and independent mechanisms

Fetus-derived DLK1 is required for maternal metabolic adaptations to pregnancy and is associated with fetal growth restriction

Trophoblast Side-Population Markers are Dysregulated in Preeclampsia and Fetal Growth Restriction

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