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Disrupted compensatory response mediated by Wolfram syndrome 1 protein and corticotrophin-releasing hormone family peptides in early-onset intrahepatic cholestasis pregnancy.

Abstract：

INTRODUCTION:The most adverse perinatal outcome of intrahepatic cholestasis of pregnancy (ICP) is sudden fetal death related to acute fetoplacental hypoxia. Corticotrophin-releasing hormone (CRH), urocortin (UCN), and Wolfram syndrome 1 (WFS1) proteins may have a compensatory response to hypoxic stress. METHODS:A total of 108 singleton pregnant women were divided into three groups: control, late-onset ICP, and early-onset ICP. Enzyme-linked immunosorbent assays were used to detected maternal serum CRH, UCN, and WFS1 levels. Western blotting and real-time polymerase chain reaction were conducted to quantify placental protein and mRNA levels of CRH, UCN, and WFS1. Pearson correlation scatterplots and Pearson correlation matrix were employed to testify the correlation. RESULTS:Placental WFS1 had a positive relation with placental UCN (r = 0.69, P < 0.05) and serum UCN (r = 0.36, P < 0.05). Placental CRH was positively correlated with maternal serum CRH (r = 0.53, P < 0.05). Maternal serum and placental levels of CRH, UCN, and WFS1 significantly increased in the early-onset ICP group compared with the control group (P < 0.05). Placental levels of UCN and WFS1 in the early-onset ICP group were significantly elevated and higher in comparison with the late-onset ICP group (P < 0.05). However, the transcriptional levels of CRH, UCN, and WFS1 were impaired in the early-onset ICP group. DISCUSSION:Our study revealed that transcription and translation of WFS1, CRH, and UCN were altered during pregnancies complicated by early-onset ICP. This disrupted compensatory response mediated by WFS1 and CRH family peptides in early-onset ICP may play a significant role in the pathogenesis of sudden fetal death in acute fetal hypoxia.

journal_name

Placenta

journal_title

Placenta

authors

Xu T,Zhou Z,Liu N,Deng C,Huang G,Zhou F,Liu X,Wang X

doi

10.1016/j.placenta.2019.06.378

subject

Has Abstract

pub_date

2019-08-01 00:00:00

pages

63-71

eissn

0143-4004

issn

1532-3102

pii

S0143-4004(18)31193-7

journal_volume

pub_type

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Disrupted compensatory response mediated by Wolfram syndrome 1 protein and corticotrophin-releasing hormone family peptides in early-onset intrahepatic cholestasis pregnancy.