Abstract：
UNASSIGNED: Preeclampsia is a significant pregnancy disorder with an unknown cause, mainly attributed to impaired spiral arterial remodeling.
UNASSIGNED: Using RNA sequencing, we identified key genes in placental tissues from healthy individuals and preeclampsia patients. Placenta and plasma samples from pregnant women were collected to detect the expression of TPBG (trophoblast glycoprotein). Pregnant rats were injected with TPBG-carrying adenovirus to detect preeclamptic features. HTR-8/SVneo cells transfected with a TPBG overexpression lentiviral vector were used in cell function experiments. The downstream molecular mechanisms of TPBG were explored using RNA sequencing and single-cell RNA sequencing data. TPBG expression was knocked down in the lipopolysaccharide-induced preeclampsia-like rat model to rescue the preeclampsia features. We also assessed TPBG\'s potential as an early preeclampsia predictor using clinical plasma samples.
UNASSIGNED: TPBG emerged as a crucial differentially expressed gene, expressed specifically in syncytiotrophoblasts and extravillous trophoblasts. Subsequently, we established a rat model with preeclampsia-like phenotypes by intravenously injecting TPBG-expressing adenoviruses, observing impaired spiral arterial remodeling, thus indicating a causal correlation between TPBG overexpression and preeclampsia. Studies with HTR-8/SVneo cells, chorionic villous explants, and transwell assays showed TPBG overexpression disrupts trophoblast/extravillous trophoblast migration/invasion and chemotaxis. Notably, TPBG knockdown alleviated the lipopolysaccharide-induced preeclampsia-like rat model. We enhanced preeclampsia risk prediction in early gestation by combining TPBG expression with established clinical predictors.
UNASSIGNED: These findings are the first to show that TPBG overexpression contributes to preeclampsia development by affecting uterine spiral artery remodeling. We propose TPBG levels in maternal blood as a predictor of preeclampsia risk. The proposed mechanism by which TPBG overexpression contributes to the occurrence of preeclampsia via its disruptive effect on trophoblast and extravillous trophoblast migration/invasion on uterine spiral artery remodeling, thereby increasing the risk of preeclampsia.
UNASSIGNED: Using RNA sequencing, we identified key genes in placental tissues from healthy individuals and preeclampsia patients. Placenta and plasma samples from pregnant women were collected to detect the expression of TPBG (trophoblast glycoprotein). Pregnant rats were injected with TPBG-carrying adenovirus to detect preeclamptic features. HTR-8/SVneo cells transfected with a TPBG overexpression lentiviral vector were used in cell function experiments. The downstream molecular mechanisms of TPBG were explored using RNA sequencing and single-cell RNA sequencing data. TPBG expression was knocked down in the lipopolysaccharide-induced preeclampsia-like rat model to rescue the preeclampsia features. We also assessed TPBG\'s potential as an early preeclampsia predictor using clinical plasma samples.
UNASSIGNED: TPBG emerged as a crucial differentially expressed gene, expressed specifically in syncytiotrophoblasts and extravillous trophoblasts. Subsequently, we established a rat model with preeclampsia-like phenotypes by intravenously injecting TPBG-expressing adenoviruses, observing impaired spiral arterial remodeling, thus indicating a causal correlation between TPBG overexpression and preeclampsia. Studies with HTR-8/SVneo cells, chorionic villous explants, and transwell assays showed TPBG overexpression disrupts trophoblast/extravillous trophoblast migration/invasion and chemotaxis. Notably, TPBG knockdown alleviated the lipopolysaccharide-induced preeclampsia-like rat model. We enhanced preeclampsia risk prediction in early gestation by combining TPBG expression with established clinical predictors.
UNASSIGNED: These findings are the first to show that TPBG overexpression contributes to preeclampsia development by affecting uterine spiral artery remodeling. We propose TPBG levels in maternal blood as a predictor of preeclampsia risk. The proposed mechanism by which TPBG overexpression contributes to the occurrence of preeclampsia via its disruptive effect on trophoblast and extravillous trophoblast migration/invasion on uterine spiral artery remodeling, thereby increasing the risk of preeclampsia.
摘要：
■先兆子痫是一种严重的妊娠疾病，原因不明，主要归因于螺旋动脉重塑受损。
■使用RNA测序，我们确定了健康个体和先兆子痫患者胎盘组织中的关键基因。收集孕妇的胎盘和血浆样品以检测TPBG（滋养层糖蛋白）的表达。妊娠大鼠注射携带TPBG的腺病毒以检测先兆子痫特征。用TPBG过表达慢病毒载体转染的HTR-8/SVneo细胞用于细胞功能实验。使用RNA测序和单细胞RNA测序数据探索TPBG的下游分子机制。在脂多糖诱导的子痫前期样大鼠模型中下调TPBG表达以挽救子痫前期特征。我们还使用临床血浆样本评估了TPBG作为早期先兆子痫预测因子的潜力。
■TPBG是一个重要的差异表达基因，在合胞体滋养层和绒毛外滋养层中特异性表达。随后，我们通过静脉注射表达TPBG的腺病毒建立了子痫前期样表型的大鼠模型，观察受损的螺旋动脉重塑，因此表明TPBG过表达与先兆子痫之间存在因果关系。HTR-8/SVneo细胞的研究，绒毛膜绒毛外植体，和transwell分析显示TPBG过表达会破坏滋养细胞/绒毛外滋养细胞的迁移/侵袭和趋化性。值得注意的是,TPBG敲低可减轻脂多糖诱导的子痫前期样大鼠模型。我们通过将TPBG表达与已确定的临床预测因子相结合，提高了妊娠早期先兆子痫的风险预测。
■这些发现首次表明TPBG过表达通过影响子宫螺旋动脉重塑而促进先兆子痫的发展。我们建议母体血液中的TPBG水平作为先兆子痫风险的预测因子。TPBG过表达通过其对滋养细胞和绒毛外滋养细胞迁移/侵入子宫螺旋动脉重塑的破坏性作用而导致先兆子痫的发生的拟议机制，从而增加先兆子痫的风险。
■使用RNA测序，我们确定了健康个体和先兆子痫患者胎盘组织中的关键基因。收集孕妇的胎盘和血浆样品以检测TPBG（滋养层糖蛋白）的表达。妊娠大鼠注射携带TPBG的腺病毒以检测先兆子痫特征。用TPBG过表达慢病毒载体转染的HTR-8/SVneo细胞用于细胞功能实验。使用RNA测序和单细胞RNA测序数据探索TPBG的下游分子机制。在脂多糖诱导的子痫前期样大鼠模型中下调TPBG表达以挽救子痫前期特征。我们还使用临床血浆样本评估了TPBG作为早期先兆子痫预测因子的潜力。
■TPBG是一个重要的差异表达基因，在合胞体滋养层和绒毛外滋养层中特异性表达。随后，我们通过静脉注射表达TPBG的腺病毒建立了子痫前期样表型的大鼠模型，观察受损的螺旋动脉重塑，因此表明TPBG过表达与先兆子痫之间存在因果关系。HTR-8/SVneo细胞的研究，绒毛膜绒毛外植体，和transwell分析显示TPBG过表达会破坏滋养细胞/绒毛外滋养细胞的迁移/侵袭和趋化性。值得注意的是,TPBG敲低可减轻脂多糖诱导的子痫前期样大鼠模型。我们通过将TPBG表达与已确定的临床预测因子相结合，提高了妊娠早期先兆子痫的风险预测。
■这些发现首次表明TPBG过表达通过影响子宫螺旋动脉重塑而促进先兆子痫的发展。我们建议母体血液中的TPBG水平作为先兆子痫风险的预测因子。TPBG过表达通过其对滋养细胞和绒毛外滋养细胞迁移/侵入子宫螺旋动脉重塑的破坏性作用而导致先兆子痫的发生的拟议机制，从而增加先兆子痫的风险。
