Angiogenesis and vasculogenesis in pregnancy

Zygmunt, Marek; Herr, F.; Münstedt, Karsten; Lang, Uwe; Liang, Olin D.

doi:10.1016/s0301-2115(03)00168-4

Cited by 407 publications

(304 citation statements)

References 96 publications

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“…At this stage, the lower level of β-hCG, which is released in particular from the syncytiotrophoblasts, in the patient groups was attributed to defective angiogenesis. Studies by Demir et al (28,29) demonstrated that, in a normal pregnancy, the villous cytotrophoblastic cells, followed by Hofbauer cells of the villus stroma, strongly express VEGF, although the villous endothelium lacked immunostaining for VEGF (10). In this study, we found that Hofbauer cells and decidual stromal cells were stained comparably in all groups.…”

Section: Discussionsupporting

confidence: 56%

“…Johns et al (23) reported that serum β-hCG levels in the first trimester were lower in pregnancies that ended in miscarriage than in those that reached term. Zygmunt et al (24) highlighted the importance of angiogenesis in early pregnancy, showing that hCG not only had a trophoblast invasion stimulating effect but also was an important angiogenic factor for the feto-maternal unit (10). Numerous studies have shown that defective vascular development underlies many early pregnancy losses and incidents of intrauterine embryonic death (7,22,25).…”

Section: Discussionmentioning

confidence: 99%

“…AFP is a protein synthesized in the yolk sac and liver of the fetus and plays an important role as a proangiogenic factor in VEGF-dependent angiogenesis, especially in the endothelial cells of the feto-maternal unit (9). There are a few papers in the literature on maternal serum AFP (MS-AFP) levels in the first trimester (9,10,12,13). Previous studies have shown that the levels of endocrinological factors, such as hCG, progesterone (14,15), pregnancy associated plasma protein-A (PAPP-A) and inhibin A (13) levels, are decreased in the first trimester in patients with symptoms of threatened miscarriage (TM) who subsequently had a complete miscarriage, compared to those with a normal obstetric outcome.…”

Section: Introductionmentioning

confidence: 99%

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Low VEGF expression in conceptus material and maternal serum AFP and levels as indicators of defective angiogenesis in first-trimester miscarriages

Kutluer¹,

Çiçek²,

Moraloğlu³

et al. 2012

J Turkish German Gynecol Assoc

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Low VEGF expression in conceptus material and maternal serum AFP and β-hCG levels as indicators of defective angiogenesis in first-trimester miscarriages Objective: The aims of this study were to assess the relationship between early miscarriages and vascular endothelial growth factor (VEGF) expression and to determine the serum levels of first-trimester maternal alpha-fetoprotein (AFP) and human chorionic gonadotropin (β-hCG) as markers of angiogenesis and predictors of abortion and intrauterine fetal loss. Material and Methods:The present study was a prospective, singlecenter, randomized controlled clinical trial. Ninety-five women who were 6-10 weeks pregnant between May and June 2010 were included in the study. The subjects were divided into three groups, i.e., incomplete abortion (IA) (n=31), intrauterine death (IU-D) (n=32) and control (elective pregnancy termination) (n=32). Feto-placental materials were compared based on immune staining for VEGF in the pathology laboratory, and maternal serum samples were tested in the hormone laboratory.Results: Serum β-hCG levels in the patient groups were significantly lower than the controls (p=0.001). The serum AFP level was lower than the controls in the IA group while it was higher than the controls in the IU-D (p=0.016). Immunohistochemistry showed that the cytotrophoblast, syncytiotrophoblast and endometrial gland epithelium were weakly stained for VEGF in the patient groups (IA and IU-D) in comparison to the control group (p=0.06, p=0.028, p=0.006). Conclusion:Early pregnancy losses are related to insufficient angiogenesis, and maternal serum AFP and β-hCG can be used as markers of angiogenesis in the first trimester.(J Turkish-German Gynecol Assoc 2012; 13: 111-7) Abstract ÖzetOriginal Investigation 111

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Low VEGF expression in conceptus material and maternal serum AFP and levels as indicators of defective angiogenesis in first-trimester miscarriages

Kutluer¹,

Çiçek²,

Moraloğlu³

et al. 2012

J Turkish German Gynecol Assoc

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“…1 PlGF is a member of the vascular endothelial growth factor (VEGF) family and is crucial in initiating and perpetuating placental angiogenesis. 2 PlGF also induces vasodilation of uterine and myometrial arteries contributing to uterine vascular remodeling 3 and is associated with the systemic maternal cardiovascular adaptations to pregnancy. 4 In preeclampsia, which affects ≈2.5% to 3.0% of pregnancies because of excessive circulating levels of soluble fms-like tyrosin kinase-1 (sFlt-1), the bioavailability of PlGF is reduced, which prevents its interactions with endothelial cell surface receptors leading to endothelial dysfunction.…”

mentioning

confidence: 99%

Fluid Shear Stress Promotes Placental Growth Factor Upregulation in Human Syncytiotrophoblast Through the cAMP–PKA Signaling Pathway

et al. 2016

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Abstract-The effects of fluid shear stress (FSS) on the human syncytiotrophoblast and its biological functions have never been studied. During pregnancy, the syncytiotrophoblast is the main source of placental growth factor (PlGF), a proangiogenic factor involved in the placental angiogenesis and the vascular adaptation to pregnancy. The role of FSS in regulating PlGF expression in syncytiotrophoblasts is unknown. We investigated the impact of FSS on the production and secretion of the PlGF by the human syncytiotrophoblasts in primary cell culture. Laminar and continuous FSS (1 dyn cm −2) was applied to human syncytiotrophoblasts cultured in a parallel-plate flow chambers. Secreted levels of PlGF, sFlt-1 (soluble fmslike tyrosin kinase-1), and prostaglandin E2 were tested by immunologic assay. PlGF levels of mRNA and intracellular protein were examined by RT-PCR and Western blot, respectively. Intracellular cAMP levels were examined by timeresolved fluorescence resonance energy transfer cAMP accumulation assay. Production of cAMP and PlGF secretion was significantly increased in FSS conditions compared with static conditions. Western blot analysis of cell extracts exposed to FSS showed an increased phosphorylation of protein kinase A substrates and cAMP response element-binding protein on serine 133. FSS-induced phosphorylation of cAMP response element-binding protein and upregulation of PlGF were prevented by inhibition of protein kinase A with H89 (3 μmol/L). FSS also triggers intracellular calcium flux, which increases the synthesis and release of prostaglandin E2. The enhanced intracellular cAMP in FSS conditions was blocked by COX1/COX2 (cyclooxygenase) inhibitors, suggesting that the increase in prostaglandin E2 production could activate the cAMP/protein kinase A pathway in an autocrine/paracrine fashion. FSS activates the cAMP/protein kinase A pathway leading to upregulation of PlGF in human syncytiotrophoblast.

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“…It also plays a critical role in oocyte maturation, decidualized endometrial vascularization, embryo implantation/development and placenta angiogenesis/vascularization in early gestation [16,24,25,47]. Inadequate angiogenesis is known to be associated with RIF in both animal [40] and human studies [21].…”

Section: Discussionmentioning

confidence: 99%

The vascular endothelial growth factor (VEGF) +405 G/C polymorphism and its relationship with recurrent implantation failure in women in an IVF programme with ICSI

Boudjenah

Molina-Gomès

Wainer

et al. 2012

J Assist Reprod Genet

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Purpose Successful embryo implantation depends on trophoblast proliferation, migration and, lastly, invasion of the endometrium (to anchor the trophoblast to the uterus). This invasion is mediated by locally produced soluble factors. Of these, vascular endothelial growth factor (VEGF) is the best characterized regulator of angiogenesis. Here, we investigate the association between the VEGF+405 C/G genotype and the recurrence of embryo implantation failure in women undergoing in vitro fertilization (IVF) program with intracytoplasmic sperm injection (ICSI). Methods Forty women with recurrent implantation failure defined by absence of pregnancy after transfer of more than 10 embryos and 131 women control, with at least one live birth after the transfer of fewer than 10 embryos were included. Genomic DNA was analysed with an allele-specific polymerase chain reaction and a Chi-2 test was used to compare the respective VEGF+405 C/G genotype frequencies in cases and controls. Results The frequency of the VEGF +405C/C genotype was higher in women with recurrent implantation failure after ICSI-embryo transfer than in controls (17.5 % and 5.3 %, respectively, p00.01). Conclusion The VEGF +405 G/C polymorphism may influence embryo implantation and VEGF+405 C/C genotype may predispose to recurrent implantation failure after ICSI-ET.

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Angiogenesis and vasculogenesis in pregnancy

Cited by 407 publications

References 96 publications

Low VEGF expression in conceptus material and maternal serum AFP and levels as indicators of defective angiogenesis in first-trimester miscarriages

Low VEGF expression in conceptus material and maternal serum AFP and levels as indicators of defective angiogenesis in first-trimester miscarriages

Fluid Shear Stress Promotes Placental Growth Factor Upregulation in Human Syncytiotrophoblast Through the cAMP–PKA Signaling Pathway

The vascular endothelial growth factor (VEGF) +405 G/C polymorphism and its relationship with recurrent implantation failure in women in an IVF programme with ICSI

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