Uteroplacental Circulation in Normal Pregnancy and Preeclampsia: Functional Adaptation and Maladaptation

Hu, Xiang‐Qun; Zhang, Li

doi:10.3390/ijms22168622

Cited by 30 publications

(21 citation statements)

References 318 publications

(400 reference statements)

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“…PE has a great impact on growth and development of the fetus, impairs the structure and function of fetal cardiovascular system or kidney, and causes hypertension. 15 Current studies suggest that the pathogenesis of PE may be related to decidual macrophage dysfunction, 16 placental angiogenesis disorder, 17 placental aging, 18 , 19 protein aggregation, and defective placental aggregation phagocytosis. 20 At the molecular level, the microRNA spectrum of blood exosomes has been used to evaluate the pathophysiology of preeclampsia and predict the disease, 21 and there are more and more studies at gene level.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Network Analysis Identifies Potential Targets for Prevention of Preeclampsia

Yu¹,

Zhao²,

Sun³

et al. 2022

IJGM

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Objective Preeclampsia (PE) is a pregnancy-specific multisystem disease as well as an important cause of maternal and perinatal death. This study aimed to analyze the placental transcriptional data and clinical information of PE patients available in the published database and predict the target genes for prevention of PE. Methods The clinical information and corresponding RNA data of PE patients were downloaded from the GEO database. Cluster analysis was performed to examine the correlation between different genotyping genes and clinical manifestations. Then, bioinformatic approaches including GO, KEGG, WGCNA, and GSEA were employed to functionally characterize candidate target genes involved in pathogenesis of PE. Results Two PE datasets GSE60438 and GSE75010 were obtained and combined, thereby providing the data of 205 samples in total (100 non-PE and 105 PE samples). After eliminating the batch effect, we grouped and analyzed the integrated data, and further performed GSEA analysis. It was found that the genes in group 1 and group 2 were different from those in normal samples. Moreover, WGCNA analysis revealed that genes in group 1 were up-regulated in turquoise module, including SASH1 , PIK3CB and FLT-1 , while genes in group 2 were up-regulated in the blue and brown modules. We further conducted GO and KEGG pathway enrichment analyses and found that the differential genes in turquoise module were mainly involved in biological processes such as small molecular catabolic process, while being highly enriched in pathways, including MAPK signaling pathway and Rap1 signaling pathway. Conclusion FLT-1 was conventionally used to predict PE risk, and sFLT-1 could also be used as an indicator to evaluate PE treatment effect. As a candidate biomarker for predicting PE, SASH1 may participate in proliferation, migration, invasion and epithelial mesenchymal transformation of human trophoblast cells by regulating MAPK pathway and Rap1 signaling pathway, thus affecting the progression of PE. The mechanism allowing PIK3CB to regulate PE development was not clear, while the gene could be another candidate biomarker for PE risk prediction. This is an exploratory study and our findings were still required verification in further studies.

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Section: Discussionmentioning

confidence: 99%

Gene Expression Network Analysis Identifies Potential Targets for Prevention of Preeclampsia

Yu¹,

Zhao²,

Sun³

et al. 2022

IJGM

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“…It is well‐known that E2 and T are associated with vascular remodeling. 40 , 41 Accordingly, abnormal E2 or T may affect the placental function and lead to PE in the early stage of placental development, but the mechanism remains to be further studied. Our study revealed that sPE may be related to the concentration of T and E2, but especially the balance of E2/T.…”

Section: Discussionmentioning

confidence: 99%

Serum estradiol to testosterone ratio as a novel predictor of severe preeclampsia in the first trimester

Shen

Cao

Yao

et al. 2022

J of Clinical Hypertension

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Preeclampsia (PE) is the most common medical complication during pregnancy and the second leading cause of maternal death worldwide. However, a better predictive model of PE remains to be explored. A total of 15 severe preeclampsia (sPE) and 75 healthy control patients were included in this study. Patient data was obtained from September 2019 to September 2021. Nuchal translucency (NT) and crown-rump length (CRL) of the fetus were acquired by ultrasound. Maternal blood samples were collected at 11 +0 to 13 +6 weeks of gestation. Chemiluminescent immunoassays were used to detect serum testosterone (T) and estradiol (E2) levels. Time-resolved fluorescence analysis was used to examine the levels of serum pregnancy-associated plasma protein A (PAPPA) and β-human chorionic gonadotrophin (β-HCG) protein. The sPE group exhibited increased T levels, and decreased E2 levels and E2/T ratios from 11 to 14 weeks of gestation, compared with the control group. E2 and the E2/T ratio showed positive linear correlation with CRL in pregnant women. Body-mass-index (BMI), T, and E2 were determined to be the main factors that affected the occurrence of sPE at the 12week gestation period time point. The receiver operating characteristic (ROC) curve revealed that the AUC of the E2/T ratio was .717. The imbalanced T and E2 levels in the patients had a specific intrinsic relevance with sPE, which suggests them as novel predictors of the sPE.

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“…It is estimated that 80% to 90% of total uteroplacental blood flow perfuses the placenta at term and the remaining supplies the myometrium [ 175 , 188 , 189 ], providing sufficient nutrient and oxygen supply for the growth of the placenta and fetus. The hemodynamic changes in the uteroplacental circulation during pregnancy are primarily achieved by uterine vascular remodeling, reduced uteroplacental vascular resistance, and the formation of the placenta [ 8 , 9 , 190 , 191 , 192 ]. Notably, a variety of functional changes contribute to the adaptation.…”

Section: Adaptation/maladaptation Of the Uteroplacental Circulation I...mentioning

confidence: 99%

“…Uteroplacental blood flow is inversely proportional to uteroplacental vascular resistance. Increased uteroplacental blood flow in pregnancy is primarily achieved by lowering uteroplacental vascular resistance owing to the structural remodeling of spiral arteries, establishment of the placenta, and vasodilation [ 8 , 9 ]. Adaptive changes in the uteroplacental circulation are impaired in pregnancy complications such as preeclampsia, fetal growth restriction (FGR, also known as intrauterine growth restriction), and gestational diabetes, leading to insufficient perfusion of the placenta [ 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Ca2+-Activated K+ Channels and the Regulation of the Uteroplacental Circulation

Zhang

2023

IJMS

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Adequate uteroplacental blood supply is essential for the development and growth of the placenta and fetus during pregnancy. Aberrant uteroplacental perfusion is associated with pregnancy complications such as preeclampsia, fetal growth restriction (FGR), and gestational diabetes. The regulation of uteroplacental blood flow is thus vital to the well-being of the mother and fetus. Ca2+-activated K+ (KCa) channels of small, intermediate, and large conductance participate in setting and regulating the resting membrane potential of vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) and play a critical role in controlling vascular tone and blood pressure. KCa channels are important mediators of estrogen/pregnancy-induced adaptive changes in the uteroplacental circulation. Activation of the channels hyperpolarizes uteroplacental VSMCs/ECs, leading to attenuated vascular tone, blunted vasopressor responses, and increased uteroplacental blood flow. However, the regulation of uteroplacental vascular function by KCa channels is compromised in pregnancy complications. This review intends to provide a comprehensive overview of roles of KCa channels in the regulation of the uteroplacental circulation under physiological and pathophysiological conditions.

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Uteroplacental Circulation in Normal Pregnancy and Preeclampsia: Functional Adaptation and Maladaptation

Cited by 30 publications

References 318 publications

Gene Expression Network Analysis Identifies Potential Targets for Prevention of Preeclampsia

Gene Expression Network Analysis Identifies Potential Targets for Prevention of Preeclampsia

Serum estradiol to testosterone ratio as a novel predictor of severe preeclampsia in the first trimester

Ca2+-Activated K+ Channels and the Regulation of the Uteroplacental Circulation

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