Abstract：
BACKGROUND: It is estimated that over 2 million cases of fetal death occur worldwide every year, but, despite the high incidence, several basic and clinical characteristics of this disorder are still unclear. Placenta is suggested to play a central role in fetal death. Placenta produces hormones, cytokines and growth factors that modulate functions of the placental-maternal unit. Fetal death has been correlated with impaired secretion of some of these regulatory factors.
OBJECTIVE: The aim of the present study was to evaluate, in placentas collected from fetal death, the gene expression of inflammatory, proliferative and protective factors.
METHODS: Cases of fetal death in singleton pregnancy were retrospectively selected, excluding pregnancies complicated by fetal anomalies, gestational diabetes, intrauterine growth restriction and moderate to severe maternal diseases. A group of placentas collected from healthy singleton term pregnancies were used as controls. Groups were compared regarding maternal and gestational age, fetal sex and birth weight. Placental mRNA expression of inflammatory (IL-6), proliferative (Activin A, TGF-β1) and regulatory (VEGF, VEGFR2, ATP-binding cassette (ABC) transporters ABCB1 and ABCG2, sphingosine 1-phosphate (S1P) signaling pathway) markers was conducted using real-time PCR. Statistical analysis and graphical representation of the data were performed using the GraphPad Prism 5 software. For the statistical analysis, Student\'s t-test was used, and P values < 0.05 were considered significant.
RESULTS: Placental mRNA expression of IL-6 and VEGFR2 resulted significantly higher in the fetal death group compared to controls (P<0.01), while activin A, ABCB1 and ABCG2 expression resulted significantly lower (P<0.01). A significant alteration in the S1P signaling pathway was found in the fetal death group, with an increased expression of the specific receptor isoforms sphingosine 1-phosphate receptor 1, 3 and 4 (S1P1, S1P3, S1P4) and of sphingosine kinase 2 (SK2), one of the enzyme isoforms responsible for S1P synthesis (P<0.01).
CONCLUSIONS: (s): The present study confirmed a significantly increased expression of placental IL-6 and VEGFR2 mRNA, and for the first time showed an increased expression of S1P receptors and SK2 as well as a decreased expression of activin A and of selected ATP-binding cassette transporters, suggesting that multiple inflammatory and protective factors are deranged in placenta of fetal death.
OBJECTIVE: The aim of the present study was to evaluate, in placentas collected from fetal death, the gene expression of inflammatory, proliferative and protective factors.
METHODS: Cases of fetal death in singleton pregnancy were retrospectively selected, excluding pregnancies complicated by fetal anomalies, gestational diabetes, intrauterine growth restriction and moderate to severe maternal diseases. A group of placentas collected from healthy singleton term pregnancies were used as controls. Groups were compared regarding maternal and gestational age, fetal sex and birth weight. Placental mRNA expression of inflammatory (IL-6), proliferative (Activin A, TGF-β1) and regulatory (VEGF, VEGFR2, ATP-binding cassette (ABC) transporters ABCB1 and ABCG2, sphingosine 1-phosphate (S1P) signaling pathway) markers was conducted using real-time PCR. Statistical analysis and graphical representation of the data were performed using the GraphPad Prism 5 software. For the statistical analysis, Student\'s t-test was used, and P values < 0.05 were considered significant.
RESULTS: Placental mRNA expression of IL-6 and VEGFR2 resulted significantly higher in the fetal death group compared to controls (P<0.01), while activin A, ABCB1 and ABCG2 expression resulted significantly lower (P<0.01). A significant alteration in the S1P signaling pathway was found in the fetal death group, with an increased expression of the specific receptor isoforms sphingosine 1-phosphate receptor 1, 3 and 4 (S1P1, S1P3, S1P4) and of sphingosine kinase 2 (SK2), one of the enzyme isoforms responsible for S1P synthesis (P<0.01).
CONCLUSIONS: (s): The present study confirmed a significantly increased expression of placental IL-6 and VEGFR2 mRNA, and for the first time showed an increased expression of S1P receptors and SK2 as well as a decreased expression of activin A and of selected ATP-binding cassette transporters, suggesting that multiple inflammatory and protective factors are deranged in placenta of fetal death.
摘要：
背景：据估计，全世界每年发生超过200万例胎儿死亡病例，但是,尽管发病率很高，该疾病的一些基本和临床特征仍不清楚。建议胎盘在胎儿死亡中起核心作用。胎盘产生激素,调节胎盘-母体单位功能的细胞因子和生长因子。胎儿死亡与这些调节因子中的一些分泌受损有关。
目的：本研究的目的是评估，从胎儿死亡中收集的胎盘，炎症的基因表达，增殖和保护因素。
方法：回顾性选择单胎妊娠死胎病例，排除妊娠合并胎儿异常，妊娠期糖尿病,宫内生长受限和中度至重度孕产妇疾病。从健康的单胎足月妊娠中收集的一组胎盘用作对照。比较两组产妇和胎龄，胎儿性别和出生体重。炎症的胎盘mRNA表达（IL-6），增殖性(激活素A，TGF-β1）和调节性（VEGF，使用实时PCR进行VEGFR2、ATP结合盒(ABC)转运蛋白ABCB1和ABCG2、鞘氨醇1-磷酸(S1P)信号通路)标记。使用GraphPadPrism5软件进行数据的统计分析和图形表示。对于统计分析，使用学生的t检验，P值<0.05被认为是显著的。
结果：胎死组胎盘IL-6和VEGFR2mRNA表达明显高于对照组（P<0.01），而激活素A,ABCB1和ABCG2表达显著降低(P<0.01)。在胎儿死亡组中发现S1P信号通路的显著改变，随着特异性受体同种型鞘氨醇1-磷酸受体1、3和4（S1P1、S1P3、S1P4）和鞘氨醇激酶2（SK2）的表达增加，负责S1P合成的酶同工型之一(P<0.01)。
结论：（s）：本研究证实胎盘IL-6和VEGFR2mRNA的表达显着增加，并且首次显示S1P受体和SK2的表达增加，以及激活素A和选定的ATP结合盒转运蛋白的表达减少，提示胎儿死亡胎盘中多种炎症和保护因素紊乱。
目的：本研究的目的是评估，从胎儿死亡中收集的胎盘，炎症的基因表达，增殖和保护因素。
方法：回顾性选择单胎妊娠死胎病例，排除妊娠合并胎儿异常，妊娠期糖尿病,宫内生长受限和中度至重度孕产妇疾病。从健康的单胎足月妊娠中收集的一组胎盘用作对照。比较两组产妇和胎龄，胎儿性别和出生体重。炎症的胎盘mRNA表达（IL-6），增殖性(激活素A，TGF-β1）和调节性（VEGF，使用实时PCR进行VEGFR2、ATP结合盒(ABC)转运蛋白ABCB1和ABCG2、鞘氨醇1-磷酸(S1P)信号通路)标记。使用GraphPadPrism5软件进行数据的统计分析和图形表示。对于统计分析，使用学生的t检验，P值<0.05被认为是显著的。
结果：胎死组胎盘IL-6和VEGFR2mRNA表达明显高于对照组（P<0.01），而激活素A,ABCB1和ABCG2表达显著降低(P<0.01)。在胎儿死亡组中发现S1P信号通路的显著改变，随着特异性受体同种型鞘氨醇1-磷酸受体1、3和4（S1P1、S1P3、S1P4）和鞘氨醇激酶2（SK2）的表达增加，负责S1P合成的酶同工型之一(P<0.01)。
结论：（s）：本研究证实胎盘IL-6和VEGFR2mRNA的表达显着增加，并且首次显示S1P受体和SK2的表达增加，以及激活素A和选定的ATP结合盒转运蛋白的表达减少，提示胎儿死亡胎盘中多种炎症和保护因素紊乱。
