Impaired Compensatory Vasodilatory Effect Mediated by Wolfram Syndrome 1 and Corticotropin-Releasing Hormone Family Peptides in 17α-Ethynylestradiol-Induced Intrahepatic Cholestasis Pregnant Rats When Under Additional Acute Hypoxia Stress

Abstract. Objective:. To investigate the possible regulatory mechanism of corticotropin-releasing hormone (CRH), urocortin (UCN), and Wolfram syndrome 1 (WFS1) in 17α-ethynylestradiol (EE)-induced intrahepatic cholestasis pregnant rats and its ischemia reperfusion (IR) model. Methods:. Pregnant rats...

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Main Authors: Tingting Xu, Daijuan Chen, Xixi Deng, Yongchi Zhan, Fan Zhou, Xiaodong Wang, Dandan Shi
Format: Article
Language:English
Published: Wolters Kluwer Health 2022-01-01
Series:Maternal-Fetal Medicine
Online Access:http://journals.lww.com/10.1097/FM9.0000000000000137
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author Tingting Xu
Daijuan Chen
Xixi Deng
Yongchi Zhan
Fan Zhou
Xiaodong Wang
Dandan Shi
author_facet Tingting Xu
Daijuan Chen
Xixi Deng
Yongchi Zhan
Fan Zhou
Xiaodong Wang
Dandan Shi
author_sort Tingting Xu
collection DOAJ
description Abstract. Objective:. To investigate the possible regulatory mechanism of corticotropin-releasing hormone (CRH), urocortin (UCN), and Wolfram syndrome 1 (WFS1) in 17α-ethynylestradiol (EE)-induced intrahepatic cholestasis pregnant rats and its ischemia reperfusion (IR) model. Methods:. Pregnant rats (n = 60) were randomly divided into four experimental groups by random number table (Control, EE, IR, and EE-IR groups), and were studied on the 17th, 19th, and 21st gestational days (GD) (n = 5 in each group at the indicated time). Growth and development indicators of fetal rats among these four groups were recorded. Enzyme-linked immunosorbent assay was employed to detect CRH, UCN, and WFS1 levels in maternal sera. Western blotting and real-time polymerase chain reaction were used to quantify placental protein and placental mRNA levels of CRH, UCN, and WFS1. Multivariate analysis of variance and least significant difference test were used to establish the group and individual comparisons. Results:. A significant difference was found in placenta weight (F = 8.10, P < 0.05), fetal rat weight (F = 40.86, P < 0.05), fetal rat length (F = 61.61, P < 0.05), and fetal rat tail length (F = 55.63, P < 0.05) among four groups on the 17th ,19th , and 21st GD.What's more, the overall differences of maternal serum UCN levels among Control, EE, IR, and EE-IR groups were significant (F = 2.48, P < 0.05). Expression of WFS1 mRNA in the EE-IR group was significantly increased and higher than Control (0.46 ± 0.15 vs. 0.24 ± 0.09, P < 0.05), EE (0.46 ± 0.15 vs. 0.17 ± 0.04, P > 0.05), and IR (0.46 ± 0.15 vs. 0.22 ± 0.15, P > 0.05) groups at 19th GD, indicating that endoplasmic reticulum stress may be activated. However, the expression of CRH (0.42 ± 0.05 vs. 0.58 ± 0.12, P < 0.05), UCN (0.43 ± 0.01 vs. 0.47 ± 0.16, P > 0.05), and WFS1 (0.57 ± 0.07 vs. 0.74 ± 0.12, P > 0.05) protein in the EE-IR group was subsided compared to the IR group at 17th GD. Conclusion:. Fetal rat growth restriction was found in the EE-induced intrahepatic cholestasis model. This study revealed that significant changes in the maternal sera level of UCN , placental level of WFS1 mRNA and placental levels of CRH, UCN, and WFS1 protein in chronic versus acute stress in a rat model of pregnancy. This suggests an impaired compensatory vasodilatory effect mediated by these factors at gene transcription and protein translation levels, following acute hypoxia stress in EE-induced intrahepatic cholestasis in pregnant rats.
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spelling doaj-art-e82b77dd3c974ff4aaa69aaa7c846adb2025-08-20T02:29:07ZengWolters Kluwer HealthMaternal-Fetal Medicine2096-69542641-58952022-01-014171610.1097/FM9.0000000000000137202201000-00003Impaired Compensatory Vasodilatory Effect Mediated by Wolfram Syndrome 1 and Corticotropin-Releasing Hormone Family Peptides in 17α-Ethynylestradiol-Induced Intrahepatic Cholestasis Pregnant Rats When Under Additional Acute Hypoxia StressTingting XuDaijuan ChenXixi DengYongchi ZhanFan ZhouXiaodong WangDandan ShiAbstract. Objective:. To investigate the possible regulatory mechanism of corticotropin-releasing hormone (CRH), urocortin (UCN), and Wolfram syndrome 1 (WFS1) in 17α-ethynylestradiol (EE)-induced intrahepatic cholestasis pregnant rats and its ischemia reperfusion (IR) model. Methods:. Pregnant rats (n = 60) were randomly divided into four experimental groups by random number table (Control, EE, IR, and EE-IR groups), and were studied on the 17th, 19th, and 21st gestational days (GD) (n = 5 in each group at the indicated time). Growth and development indicators of fetal rats among these four groups were recorded. Enzyme-linked immunosorbent assay was employed to detect CRH, UCN, and WFS1 levels in maternal sera. Western blotting and real-time polymerase chain reaction were used to quantify placental protein and placental mRNA levels of CRH, UCN, and WFS1. Multivariate analysis of variance and least significant difference test were used to establish the group and individual comparisons. Results:. A significant difference was found in placenta weight (F = 8.10, P < 0.05), fetal rat weight (F = 40.86, P < 0.05), fetal rat length (F = 61.61, P < 0.05), and fetal rat tail length (F = 55.63, P < 0.05) among four groups on the 17th ,19th , and 21st GD.What's more, the overall differences of maternal serum UCN levels among Control, EE, IR, and EE-IR groups were significant (F = 2.48, P < 0.05). Expression of WFS1 mRNA in the EE-IR group was significantly increased and higher than Control (0.46 ± 0.15 vs. 0.24 ± 0.09, P < 0.05), EE (0.46 ± 0.15 vs. 0.17 ± 0.04, P > 0.05), and IR (0.46 ± 0.15 vs. 0.22 ± 0.15, P > 0.05) groups at 19th GD, indicating that endoplasmic reticulum stress may be activated. However, the expression of CRH (0.42 ± 0.05 vs. 0.58 ± 0.12, P < 0.05), UCN (0.43 ± 0.01 vs. 0.47 ± 0.16, P > 0.05), and WFS1 (0.57 ± 0.07 vs. 0.74 ± 0.12, P > 0.05) protein in the EE-IR group was subsided compared to the IR group at 17th GD. Conclusion:. Fetal rat growth restriction was found in the EE-induced intrahepatic cholestasis model. This study revealed that significant changes in the maternal sera level of UCN , placental level of WFS1 mRNA and placental levels of CRH, UCN, and WFS1 protein in chronic versus acute stress in a rat model of pregnancy. This suggests an impaired compensatory vasodilatory effect mediated by these factors at gene transcription and protein translation levels, following acute hypoxia stress in EE-induced intrahepatic cholestasis in pregnant rats.http://journals.lww.com/10.1097/FM9.0000000000000137
spellingShingle Tingting Xu
Daijuan Chen
Xixi Deng
Yongchi Zhan
Fan Zhou
Xiaodong Wang
Dandan Shi
Impaired Compensatory Vasodilatory Effect Mediated by Wolfram Syndrome 1 and Corticotropin-Releasing Hormone Family Peptides in 17α-Ethynylestradiol-Induced Intrahepatic Cholestasis Pregnant Rats When Under Additional Acute Hypoxia Stress
Maternal-Fetal Medicine
title Impaired Compensatory Vasodilatory Effect Mediated by Wolfram Syndrome 1 and Corticotropin-Releasing Hormone Family Peptides in 17α-Ethynylestradiol-Induced Intrahepatic Cholestasis Pregnant Rats When Under Additional Acute Hypoxia Stress
title_full Impaired Compensatory Vasodilatory Effect Mediated by Wolfram Syndrome 1 and Corticotropin-Releasing Hormone Family Peptides in 17α-Ethynylestradiol-Induced Intrahepatic Cholestasis Pregnant Rats When Under Additional Acute Hypoxia Stress
title_fullStr Impaired Compensatory Vasodilatory Effect Mediated by Wolfram Syndrome 1 and Corticotropin-Releasing Hormone Family Peptides in 17α-Ethynylestradiol-Induced Intrahepatic Cholestasis Pregnant Rats When Under Additional Acute Hypoxia Stress
title_full_unstemmed Impaired Compensatory Vasodilatory Effect Mediated by Wolfram Syndrome 1 and Corticotropin-Releasing Hormone Family Peptides in 17α-Ethynylestradiol-Induced Intrahepatic Cholestasis Pregnant Rats When Under Additional Acute Hypoxia Stress
title_short Impaired Compensatory Vasodilatory Effect Mediated by Wolfram Syndrome 1 and Corticotropin-Releasing Hormone Family Peptides in 17α-Ethynylestradiol-Induced Intrahepatic Cholestasis Pregnant Rats When Under Additional Acute Hypoxia Stress
title_sort impaired compensatory vasodilatory effect mediated by wolfram syndrome 1 and corticotropin releasing hormone family peptides in 17α ethynylestradiol induced intrahepatic cholestasis pregnant rats when under additional acute hypoxia stress
url http://journals.lww.com/10.1097/FM9.0000000000000137
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AT daijuanchen impairedcompensatoryvasodilatoryeffectmediatedbywolframsyndrome1andcorticotropinreleasinghormonefamilypeptidesin17aethynylestradiolinducedintrahepaticcholestasispregnantratswhenunderadditionalacutehypoxiastress
AT xixideng impairedcompensatoryvasodilatoryeffectmediatedbywolframsyndrome1andcorticotropinreleasinghormonefamilypeptidesin17aethynylestradiolinducedintrahepaticcholestasispregnantratswhenunderadditionalacutehypoxiastress
AT yongchizhan impairedcompensatoryvasodilatoryeffectmediatedbywolframsyndrome1andcorticotropinreleasinghormonefamilypeptidesin17aethynylestradiolinducedintrahepaticcholestasispregnantratswhenunderadditionalacutehypoxiastress
AT fanzhou impairedcompensatoryvasodilatoryeffectmediatedbywolframsyndrome1andcorticotropinreleasinghormonefamilypeptidesin17aethynylestradiolinducedintrahepaticcholestasispregnantratswhenunderadditionalacutehypoxiastress
AT xiaodongwang impairedcompensatoryvasodilatoryeffectmediatedbywolframsyndrome1andcorticotropinreleasinghormonefamilypeptidesin17aethynylestradiolinducedintrahepaticcholestasispregnantratswhenunderadditionalacutehypoxiastress
AT dandanshi impairedcompensatoryvasodilatoryeffectmediatedbywolframsyndrome1andcorticotropinreleasinghormonefamilypeptidesin17aethynylestradiolinducedintrahepaticcholestasispregnantratswhenunderadditionalacutehypoxiastress