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Beihua Kong - One of the best experts on this subject based on the ideXlab platform.
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association of dll4 notch and hif 1a vegf signaling in the angiogenesis of Missed Abortion
PLOS ONE, 2013Co-Authors: Yan Fang, Chunyan Ji, Shuang Yu, Beihua KongAbstract:Background Dll4/Notch and HIF-1a-VEGF have been shown to play an important role during angiogenesis, but there are no data about their roles and association in Missed Abortion. In this study, we investigated the association of Dll4/Notch and HIF-1a-VEGF signaling in Missed Abortion. Methods Women with Missed Abortion (n = 27) and healthy controls (n = 26) were included in the study. Real-time Reverse Transcription-PCR Analyses (RT-PCR) was used to analyze the mRNA levels of Dll4/Notch and HIF-1a-VEGF signaling molecules. The protein level for Dll4 was measured by immunohistochemistry. Results Compared with induced Abortion, the expression of VEGF was statistically reduced while the level of VEGFR1 and Notch1 was significantly up-regulated in Missed Abortion. Though other molecules (VEGFR2 and Dll4) were marginally higher in Missed Abortion, no statistical difference was observed. The expression of HIF-1a was significantly up-regulated, and close negatively correlated with VEGF in Missed Abortion. Both in induced Abortion and Missed Abortion, Dll4 was positively correlated with Notch1. Conclusions The early pregnancy is in a hypoxic environment, this may encourage the angiogenesis, but severe hypoxic may inhibit the angiogenesis. Aberrant Dll4/Notch and HIF-1a-VEGF signaling may have a role in Missed Abortion.
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the p53 hdm2 gene gene polymorphism interaction is associated with the development of Missed Abortion
Human Reproduction, 2011Co-Authors: Yan Fang, Beihua Kong, Qifeng YangAbstract:BACKGROUND: The interaction between p53 and human double minute 2 (HDM2) plays an important role in apoptosis; therefore, functional polymorphisms in these genes might have adverse effects in early pregnancy. In this study, we investigated whether p53 codon 72 and HDM2 promoter (SNP309) polymorphisms were associated with the development of Missed Abortion. METHODS: Women with Missed Abortions (n = 60) and healthy controls (n = 64) were included in the study. Genotyping of the p53 codon 72 and HDM2 SNP309 (T. G) polymorphisms was performed by PCR with sequence-specific primers and PCR-restriction fragment length polymorphism analysis, respectively, using villous samples. The mRNA and protein levels for p53 and HDM2 were measured by real-time PCR and semi-quantitative immunohistochemistry, respectively. RESULTS: For the p53 codon 72 polymorphism, no difference in genotype or allele frequencies was observed in women with Missed Abortion versus controls. However, for the HDM2 SNP309 (T. G) polymorphism, G/G genotype was associated with a higher risk of Missed Abortion compared with the T/T + T/G genotypes (P = 0.043). Women carrying the HDM2 G/G genotype or p53 Pro/Pro genotype had higher HDM2 mRNA (P = 0.04 and P = 0.013, respectively) and protein (P = 0.001 and P = 0.037, respectively) levels than women with other HDM2 SNP309 and p53 codon 72 genotypes. CONCLUSIONS: The genotypes HDM2 SNP309 G/G and p53 codon 72 Pro/Pro can induce high levels of HDM2, which may be associated with Missed Abortion.
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mdm2 309 polymorphism is associated with Missed Abortion
Human Reproduction, 2009Co-Authors: Yan Fang, Beihua Kong, Qifeng YangAbstract:background: In this study, we assessed whether the single nucleotide polymorphism in the murine double minute 2 (MDM2) promoter (SNP309) was associated with the occurrence of Missed Abortion. methods: Genotyping of MDM2 SNP309 polymorphism was conducted by polymerase chain reaction-restriction fragment length polymorphism with blood and villous samples from 95 women diagnosed as having 1st trimester Missed Abortion. results: The MDM2 SNP309 G/G genotype was associated with a higher risk of Missed Abortion compared with the T/T þ T/G genotype in blood (P ¼ 0.010; odds ratio (OR): 2.164; 95% confidence interval (CI): 1.207 –3.878) and villous samples (P ¼ 0.043; OR: 2.767; 95% CI: 1.092 –7.011). conclusions: The MDM2 SNP309 G/G genotype may be a genetic risk factor for Missed Abortion.
Yan Fang - One of the best experts on this subject based on the ideXlab platform.
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association of β arrestin1 and p53 mdm2 signaling in the development of Missed Abortion
Journal of Obstetrics and Gynaecology Research, 2021Co-Authors: Ting Liu, Qihui Yin, Huanyu Zhou, Yan FangAbstract:Background Missed Abortion is a peculiar form of spontaneous Abortion before 20 weeks' gestation. The definite etiology and pathogenesis are not fully understood. Recent studies have demonstrated that p53/Mdm2-mediated ubiquitination of the IGF-1R may be closely related to G-protein-coupled receptor kinases (GRK)/β-arrestin1 system. Our previous studies have confirmed that the elevated expression of p53 and Mdm2 may be responsible for apoptosis during Missed Abortion. However, there was no information surrounding β-arrestin1 in Missed Abortion. Methods The mRNA levels of β-arrestin1 in villous samples of 30 Missed Abortion patients and 31 healthy controls were determined by real-time quantitative polymerase chain reaction (PCR). Immunohistochemistry was used to explore the expression and location of β-arrestin1, p53, Mdm2, VEGF and HIF-lα in trophoblasts. Transwell assays were performed to examine the influences of β-arrestin1 expression on cell invasion. Furthermore, we tested the effect of β-arrestin1 on the expression of p53, Mdm2, ERK, AKT and NF-κB. Results The expression of β-arrestin1 in the villous samples of Missed Abortion group was dramatically lower than control group by quantitative real-time-PCR and immunohistochemistry. Furthermore, the patients with Missed Abortion showed significantly higher levels of p53, Mdm2, HIF-lα and lower level of VEGF than healthy controls by immunohistochemistry. Functional studies showed that suppression of β-arrestin1 in HTR-8 cells inhibited cell invasion. The protein expressions of ERK and AKT in HTR-8 cells were significantly downregulated by reducing the expression of β-arrestin1, while the expressions of p53, Mdm2, NF-κB were enhanced. Overexpression of β-arrestin1 exhibited the adverse effect. Conclusion Our data indicated that β-arrestin1 play an important role in maintaining the maternal-fetal tolerance, the decreased expression of β-arrestin1 in the villous samples may be related with the development of Missed Abortion.
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association of dll4 notch and hif 1a vegf signaling in the angiogenesis of Missed Abortion
PLOS ONE, 2013Co-Authors: Yan Fang, Chunyan Ji, Shuang Yu, Beihua KongAbstract:Background Dll4/Notch and HIF-1a-VEGF have been shown to play an important role during angiogenesis, but there are no data about their roles and association in Missed Abortion. In this study, we investigated the association of Dll4/Notch and HIF-1a-VEGF signaling in Missed Abortion. Methods Women with Missed Abortion (n = 27) and healthy controls (n = 26) were included in the study. Real-time Reverse Transcription-PCR Analyses (RT-PCR) was used to analyze the mRNA levels of Dll4/Notch and HIF-1a-VEGF signaling molecules. The protein level for Dll4 was measured by immunohistochemistry. Results Compared with induced Abortion, the expression of VEGF was statistically reduced while the level of VEGFR1 and Notch1 was significantly up-regulated in Missed Abortion. Though other molecules (VEGFR2 and Dll4) were marginally higher in Missed Abortion, no statistical difference was observed. The expression of HIF-1a was significantly up-regulated, and close negatively correlated with VEGF in Missed Abortion. Both in induced Abortion and Missed Abortion, Dll4 was positively correlated with Notch1. Conclusions The early pregnancy is in a hypoxic environment, this may encourage the angiogenesis, but severe hypoxic may inhibit the angiogenesis. Aberrant Dll4/Notch and HIF-1a-VEGF signaling may have a role in Missed Abortion.
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the p53 hdm2 gene gene polymorphism interaction is associated with the development of Missed Abortion
Human Reproduction, 2011Co-Authors: Yan Fang, Beihua Kong, Qifeng YangAbstract:BACKGROUND: The interaction between p53 and human double minute 2 (HDM2) plays an important role in apoptosis; therefore, functional polymorphisms in these genes might have adverse effects in early pregnancy. In this study, we investigated whether p53 codon 72 and HDM2 promoter (SNP309) polymorphisms were associated with the development of Missed Abortion. METHODS: Women with Missed Abortions (n = 60) and healthy controls (n = 64) were included in the study. Genotyping of the p53 codon 72 and HDM2 SNP309 (T. G) polymorphisms was performed by PCR with sequence-specific primers and PCR-restriction fragment length polymorphism analysis, respectively, using villous samples. The mRNA and protein levels for p53 and HDM2 were measured by real-time PCR and semi-quantitative immunohistochemistry, respectively. RESULTS: For the p53 codon 72 polymorphism, no difference in genotype or allele frequencies was observed in women with Missed Abortion versus controls. However, for the HDM2 SNP309 (T. G) polymorphism, G/G genotype was associated with a higher risk of Missed Abortion compared with the T/T + T/G genotypes (P = 0.043). Women carrying the HDM2 G/G genotype or p53 Pro/Pro genotype had higher HDM2 mRNA (P = 0.04 and P = 0.013, respectively) and protein (P = 0.001 and P = 0.037, respectively) levels than women with other HDM2 SNP309 and p53 codon 72 genotypes. CONCLUSIONS: The genotypes HDM2 SNP309 G/G and p53 codon 72 Pro/Pro can induce high levels of HDM2, which may be associated with Missed Abortion.
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mdm2 309 polymorphism is associated with Missed Abortion
Human Reproduction, 2009Co-Authors: Yan Fang, Beihua Kong, Qifeng YangAbstract:background: In this study, we assessed whether the single nucleotide polymorphism in the murine double minute 2 (MDM2) promoter (SNP309) was associated with the occurrence of Missed Abortion. methods: Genotyping of MDM2 SNP309 polymorphism was conducted by polymerase chain reaction-restriction fragment length polymorphism with blood and villous samples from 95 women diagnosed as having 1st trimester Missed Abortion. results: The MDM2 SNP309 G/G genotype was associated with a higher risk of Missed Abortion compared with the T/T þ T/G genotype in blood (P ¼ 0.010; odds ratio (OR): 2.164; 95% confidence interval (CI): 1.207 –3.878) and villous samples (P ¼ 0.043; OR: 2.767; 95% CI: 1.092 –7.011). conclusions: The MDM2 SNP309 G/G genotype may be a genetic risk factor for Missed Abortion.
Jia Chen - One of the best experts on this subject based on the ideXlab platform.
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the role of β hcg and vegf mek erk signaling pathway in villi angiogenesis in patients with Missed Abortion
Placenta, 2021Co-Authors: Guangzhuang Jing, Jianling Yao, Yuhui Dang, Weitao Liang, Liao Xie, Jia ChenAbstract:Abstract Objective To analyze the effects of the Human Chorionic Gonadotropin beta (β-hCG) and the VEGF-MEK/ERK signaling pathway on villi angiogenesis in early Missed Abortion. Methods A total of 12 cases of women with Missed Abortion and 12 cases of women who had induced Abortion voluntarily without any disease were included in the present study. The age, pregnancy time and gestation period in the control group corresponded to the Missed Abortion group. Wes Simple Western system and qRT-PCR were used to detect the expression of VEGF-MEK/ERK signaling pathway related proteins and genes in villous. Radioimmunoassay and Enzyme-linked immunosorbent assay were used to detect β-hCG and VEGF levels in serum. The microvascular density (MVD) in villous tissue was analyzed by immunohistochemical staining. Results The levels of β-hCG and VEGF in serum, the expression of VEGF-MEK/ERK signaling pathway and MVD in villous tissue of the Missed Abortion group were lower than those of the control group. In addition, compared with the control group, the layers of trophoblasts of the villous tissue in the Missed Abortion group became thinner significantly, the number of cells reduced, the cell structures were disorganized, and parts of the trophoblast cells were absent. Correlational analysis showed that the protein expression of ERK1/2 was positively correlated with MVD in Missed Abortion group. Conclusions Our results reveal that decreased production of β-hCG in early pregnant women could down-regulate the expression of VEGF-MEK/ERK signal pathway, then reduce angiogenesis and eventually leading to the abnormal angiogenesis of villous, which may be an important mechanism of Missed Abortion.
Daniel Rukavina - One of the best experts on this subject based on the ideXlab platform.
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Granulysin-mediated apoptosis of trophoblasts in blighted ovum and Missed Abortion.
American journal of reproductive immunology (New York N.Y. : 1989), 2018Co-Authors: Tamara Gulic, Gordana Laškarin, Marin Dominovic, Lana Glavan Gacanin, Emina Babarović, Zeljka Rubesa, Herman Haller, Daniel RukavinaAbstract:Problem Granulysin (GNLY) is a cytotoxic molecule mostly present in decidual natural killer (NK) cells. Blighted ovum (BO) and Missed Abortion (MA) represent the early pathological pregnancies with hindered development of the embryoblast or a dead embryo. We investigated the GNLY-mediated apoptotic mechanism potentially responsible for delayed termination of pregnancy. Method of study We performed immunohistological and immunofluorescence labeling of decidual tissues (GNLY, Apaf-1, NF-κB). NKG2A expression was analyzed by flow cytometry and GNLY mRNA by RT-qPCR. Results The GNLY labeling intensity (H score) was lower in the nuclei of trophoblast cells in BO and MA. GNLY gene levels were inversely detected in BO and MA. A decreased decidual NK cell percentage was found in MA. NK cells from pathological pregnancies expressed lower NKG2A levels. The highest frequency of Apaf-1 was found in trophoblast cells of MA. NF-kB was highly expressed in decidual cells of BO. Conclusion The reduced activation of GNLY-mediated killing might be implicated in the slower rejection of trophoblast cells in BO and MA. A decreased authentic decidual NK cell number could be responsible for low cytotoxicity against trophoblast cells in MA. In BO, trophoblast cells have a higher survival potential due to increased NF-kB expression.
Shuang Yu - One of the best experts on this subject based on the ideXlab platform.
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association of dll4 notch and hif 1a vegf signaling in the angiogenesis of Missed Abortion
PLOS ONE, 2013Co-Authors: Yan Fang, Chunyan Ji, Shuang Yu, Beihua KongAbstract:Background Dll4/Notch and HIF-1a-VEGF have been shown to play an important role during angiogenesis, but there are no data about their roles and association in Missed Abortion. In this study, we investigated the association of Dll4/Notch and HIF-1a-VEGF signaling in Missed Abortion. Methods Women with Missed Abortion (n = 27) and healthy controls (n = 26) were included in the study. Real-time Reverse Transcription-PCR Analyses (RT-PCR) was used to analyze the mRNA levels of Dll4/Notch and HIF-1a-VEGF signaling molecules. The protein level for Dll4 was measured by immunohistochemistry. Results Compared with induced Abortion, the expression of VEGF was statistically reduced while the level of VEGFR1 and Notch1 was significantly up-regulated in Missed Abortion. Though other molecules (VEGFR2 and Dll4) were marginally higher in Missed Abortion, no statistical difference was observed. The expression of HIF-1a was significantly up-regulated, and close negatively correlated with VEGF in Missed Abortion. Both in induced Abortion and Missed Abortion, Dll4 was positively correlated with Notch1. Conclusions The early pregnancy is in a hypoxic environment, this may encourage the angiogenesis, but severe hypoxic may inhibit the angiogenesis. Aberrant Dll4/Notch and HIF-1a-VEGF signaling may have a role in Missed Abortion.