Intrahepatic cholestasis of pregnancy: new insights into its pathogenesis

Floreani, Annarosa; Caroli, D.; Lazzari, Roberta; Memmo, A.; Vidali, E.; Colavito, Davide; D’Arrigo, Antonello; Leon, A.; Romero, Roberto; Gervasi, Maria Teresa

doi:10.3109/14767058.2013.783810

Cited by 27 publications

(20 citation statements)

References 34 publications

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“…ICP has a complex etiology including genetic factors, endocrine factors, and the impact of pregnancy on FXR function (Abu-Hayyeh, Papacleovoulou & Williamson, 2013; Floreani et al, 2013). The present study focused on FXR-SHP regulation under physiological conditions.…”

Section: Discussionmentioning

confidence: 99%

“…The etiology and pathogenesis of ICP are still not clear, but many studies have related this disease to abnormal bile acid metabolism (Abu-Hayyeh, Papacleovoulou & Williamson, 2013; Floreani et al, 2013). ICP with elevated bile acids in serum and liver is a major cause for premature embryo development and embryonic death (Diken, Usta & Nassar, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Hepatic bile acids and bile acid-related gene expression in pregnant and lactating rats

Xie

Zhang

Liu

et al. 2013

PeerJ

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Background. Significant physiological changes occur during pregnancy and lactation. Intrahepatic cholestasis of pregnancy (ICP) is a liver disease closely related to disruption of bile acid homeostasis. The objective of this study was to examine the regulation of bile acid synthesis and transport in normal pregnant and lactating rats.Materials and Methods. Livers from timed pregnant SD rats were collected on gestational days (GD) 10, 14 and 19, and postnatal days (PND) 1, 7, 14 and 21. Total bile acids were determined by the enzymatic method, total RNA was isolated and subjected to real time RT-PCR analysis. Liver protein was extracted for western-blot analysis.Results. Under physiological conditions hepatic bile acids were not elevated during pregnancy but increased during lactation in rats. Bile acid synthesis rate-limiting enzyme Cyp7a1 was unchanged on gestational days, but increased on PND14 and 21 at mRNA and protein levels. Expression of Cyp8b1, Cyp27a1 and Cyp7b1 was also higher during lactation. The mRNA levels of small heterodimer partner (SHP) and protein levels of farnesoid X receptor (FXR) were increased during pregnancy and lactation. Bile acid transporters Ntcp, Bsep, Mrp3 and Mrp4 were lower at gestation, but increased during lactation. Hepatic Oatp transporters were decreased during pregnancy and lactation.Conclusion. Hepatic bile acid homeostasis is maintained during normal pregnancy in rats, probably through the FXR-SHP regulation. The expression of bile acid synthesis genes and liver bile acid accumulation were increased during lactation, together with increased expression of bile acid efflux transporter Bsep, Mrp3 and Mrp4.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hepatic bile acids and bile acid-related gene expression in pregnant and lactating rats

Xie

Zhang

Liu

et al. 2013

PeerJ

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“…Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-related syndrome characterized by pruritus and elevated serum levels of liver enzymes and/or bile acids; the incidence varies geographically from 0.1 to 15.6% [1]. ICP is associated with increased risks of perinatal complications, including spontaneous preterm labor, fetal distress, and sudden intrauterine death [2].…”

Section: Introductionmentioning

confidence: 99%

The Serum microRNA Profile of Intrahepatic Cholestasis of Pregnancy: Identification of Novel Noninvasive Biomarkers

Zou¹,

Luo²,

Zhao³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific disease that significantly increases the risk of fetal complications. Here, we measured serum miRNA levels in ICP patients to identify candidate biomarkers for ICP. Methods: We used the Agilent miRNA array followed by reverse transcription-polymerase chain reaction assays to identify and validate the serum miRNA profiles of 40 pregnant women with ICP and 40 healthy pregnant controls. We used bioinformatics to identify metabolic processes related to differentially expressed miRNAs. Results: The expression levels of three miRNAs (miR-371a- 5p, miR-6865-5p, and miR-1182) were significantly increased in ICP patients compared to controls; the areas under the receiver operating characteristic (ROC) curves (AUCs) were 0.771, 0.811, and 0.798, respectively. Multiple logistic regression analysis showed that a combination of the levels of the three miRNAs afforded a greater AUC (0.845), thus more reliably diagnosing ICP. The levels of all three miRNAs were positively associated with that of total bile acids. Furthermore, bioinformatics analysis indicated that the three miRNAs principally affected lipid phosphorylation, apoptosis, and the MAPK signaling pathway. Conclusion: This preliminary work improves our understanding of serum miRNA changes in pregnant women with ICP. The three miRNAs may serve as novel noninvasive biomarkers of ICP.

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“…Mutations in the genes responsible for bile formation, including ACBC11 (bile salt export pump) and ABCB4 (MDR3), significantly increase a woman's chance of developing ICP, as well as other hepatobiliary diseases. Floreani et al () found that GABRA 2 was upregulated in ICP and this was involved in the pathophysiology of the pruritus experienced by women with this disorder.…”

Section: A Complex Disordermentioning

confidence: 99%