A placental phenotype for intrahepatic cholestasis of pregnancy

Geenes, Victoria; Yh, Lim; Bowman, Natalie M.; Tailor, Hiren; Dixon, Peter H.; Chambers, Jenny; Brown, Laura D.; Wyatt-Ashmead, Josephine; Bhakoo, Kishore; Williamson, Catherine

doi:10.1016/j.placenta.2011.09.006

Cited by 70 publications

(41 citation statements)

References 33 publications

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“…Villous explant culture from the term placenta was performed according to previous reports4849. In brief, fresh human term placental tissues were collected from healthy women with pregnancy (37–39 gestational weeks) The villi were collected and dissected into small pieces.…”

Section: Methodsmentioning

confidence: 99%

Downregulation of peroxiredoxin-3 by hydrophobic bile acid induces mitochondrial dysfunction and cellular senescence in human trophoblasts

Menon

et al. 2016

Sci Rep

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Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific disorder characterised by raised bile acids in foetal-maternal circulation, which threatens perinatal health. During the progression of ICP, the effect of oxidative stress is underscored. Peroxiredoxin-3 (PRDX3) is a mitochondrial antioxidant enzyme that is crucial to balance intracellular oxidative stress. However, the role of PRDX3 in placental trophoblast cells under ICP is not fully understood. We demonstrated that the level of PRDX3 was downregulated in ICP placentas as well as bile acids–treated trophoblast cells and villous explant in vitro. Toxic levels of bile acids and PRDX3 knockdown induced oxidative stress and mitochondrial dysfunction in trophoblast cells. Moreover, silencing of PRDX3 in trophoblast cell line HTR8/SVneo induced growth arrest and cellular senescence via activation of p38-mitogen-activated protein kinase (MAPK) and induction of p21WAF1/CIP and p16INK4A. Additionally, enhanced cellular senescence, determined by senescence-associated beta-galactosidase staining, was obviously attenuated by p38-MAPK inhibitor SB203580. Our data determined that exposure to bile acid decreased PRDX3 level in human trophoblasts. PRDX3 protected trophoblast cells against mitochondrial dysfunction and cellular senescence induced by oxidative stress. Our results suggest that decreased PRDX3 by excessive bile acids in trophoblasts plays a critical role in the pathogenesis and progression of ICP.

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Section: Methodsmentioning

confidence: 99%

Downregulation of peroxiredoxin-3 by hydrophobic bile acid induces mitochondrial dysfunction and cellular senescence in human trophoblasts

Menon

et al. 2016

Sci Rep

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“…Moreover, a role for the placenta in the development of ICP has been suggested, due to the disappearance of pruritus and the normalization of liver function tests after delivery of the placenta [9], [10]. Studies have also shown that high concentrations of bile acids can induce apoptosis in the placenta, and the incidence of apoptosis decreases after treatment with ursodeoxycholic acid (UDCA), which protects the placenta from the toxic effect of bile acids and commonly used in the management of ICP [9], [11]. All these findings suggest that a high concentration of bile acids may play a key role in damage to the placenta, and also participate in the molecular pathogenesis of ICP and the incidence of adverse fetal outcomes.…”

Section: Introductionmentioning

confidence: 99%

Comparative Proteomics Analysis of Placenta from Pregnant Women with Intrahepatic Cholestasis of Pregnancy

Zhang

Guo

et al. 2013

PLoS ONE

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IntroductionIntrahepatic cholestasis of pregnancy (ICP) usually occurs in the third trimester and associated with increased risks in fetal complications. Currently, the exact cause of this disease is unknown. In this study we aim to investigate the potential proteins in placenta, which may participate in the molecular mechanisms of ICP-related fetal complications using iTRAQ-based proteomics approach.MethodsThe iTRAQ analysis combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to separate differentially expressed placental proteins from 4 pregnant women with ICP and 4 healthy pregnant women. Bioinformatics analysis was used to find the relative processes that these differentially expressed proteins were involved in. Three apoptosis related proteins ERp29, PRDX6 and MPO that resulted from iTRAQ-based proteomics were further verified in placenta by Western blotting and immunohistochemistry. Placental apoptosis was also detected by TUNEL assay.ResultsProteomics results showed there were 38 differentially expressed proteins from pregnant women with ICP and healthy pregnant women, 29 were upregulated and 9 were downregulated in placenta from pregnant women with ICP. Bioinformatics analysis showed most of the identified proteins was functionally related to specific cell processes, including apoptosis, oxidative stress, lipid metabolism. The expression levels of ERp29, PRDX6 and MPO were consistent with the proteomics data. The apoptosis index in placenta from ICP patients was significantly increased.ConclusionThis preliminary work provides a better understanding of the proteomic alterations of placenta from pregnant women with ICP and may provide us some new insights into the pathophysiology and potential novel treatment targets for ICP.

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“…During pregnancy, the placenta as a bile acid barrier and the excretion of bile acids mainly depends on the placenta [25] [26]. There are several papers showed that placentas from women with ICP are associated with morphological abnormalities, such as increased occurrence of syncytial knots, thought to represent areas of apoptosis, reduced intervillous space and smaller blood vessels [27] [28] [29]. In our results, we also observed the morphological changes in placenta of patients with ICP.…”

Section: Discussionmentioning

confidence: 99%

Bile Acid Effects on Placental Damage in Intrahepatic Cholestasis of Pregnancy

Xie¹,

Liu²,

Xiao³

et al. 2018

JBM

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Aims: The abnormal increase of bile acid is found in intrahepatic cholestasis of pregnancy (ICP). It also can be observed the damage of placental tissue in ICP. The aim of this study was to find the associations of the bile acid in umbilical vein and the damage of placental tissue. Methods: Thirty women diagnosed with ICP and fifty normal pregnant women between September 2015 and September 2017 at Nanshan District Maternity & Child Healthcare Hospital of Shenzhen were included in this study. The glycocholic acid (GA), total bile acids (TBA), total bilirubin (TB), direct bilirubin (DB) and albumin level in umbilical vein were measured by cycle enzyme method in ICP and control group. The placental damage was analyzed by morphologic study using hematoxylin dyes in two groups. The correlation between the level of the bile acid in the umbilical vein and the damage of the placenta was assessed using SPSS software. Results: The GA, TBA, TB, DB and albumin level in umbilical vein were significantly higher in ICP than those of pregnant women, respectively. The placental villis were expanded and the structure was destroyed in ICP. The vessel was damaged and the cell trophoblast hyperplasia in ICP. It also can be seen that there was obvious nodules and a typical fibrous necrotic substance in ICP but not in control group. There is a positive correlation between the level of the TBA in the umbilical vein and the damage of the placenta in ICP. Conclusion: The TBAs were significantly higher in umbilical vein and were related to the placental damage in ICP.

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A placental phenotype for intrahepatic cholestasis of pregnancy

Cited by 70 publications

References 33 publications

Downregulation of peroxiredoxin-3 by hydrophobic bile acid induces mitochondrial dysfunction and cellular senescence in human trophoblasts

Downregulation of peroxiredoxin-3 by hydrophobic bile acid induces mitochondrial dysfunction and cellular senescence in human trophoblasts

Comparative Proteomics Analysis of Placenta from Pregnant Women with Intrahepatic Cholestasis of Pregnancy

Bile Acid Effects on Placental Damage in Intrahepatic Cholestasis of Pregnancy

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