ffects of Exposure to Monocrotaline on Cholesterol Levels of Fetal Rats

Chinese Journal of Pharmacovigilance ›› 2019, Vol. 16 ›› Issue (2): 71-75.

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ffects of Exposure to Monocrotaline on Cholesterol Levels of Fetal Rats

GUO Qi^1,2, WANG Yanqing³, CHENG Yanxiang³, LIU Jie^1,2, QIU Shuaikai^1,2, XIANG E^1,2, WANG Hui^1,2, GUO Yu^1,2,*

1 Department of Pharmacology, Basic Medical School of Wuhan University, Hubei Wuhan 430071, China;
2 Hubei Provincial Key Laboratory of Developmentally Originated Disease, Hubei Wuhan 430071, China;
3 Department of Gynecology, Renming Hospital of Wuhan University, Hubei Wuhan 430060, China

Received:2019-03-12 Revised:2019-03-12 Online:2019-02-25 Published:2019-03-12
Contact: *郭喻,女,副教授,发育毒理学。E-mail：guoy@whu.edu.cn
Supported by:
国家自然科学基金（81473290）：吡咯里西啶生物碱致母、胎肝毒性差异及其代谢活化机制; 国家自然科学基金青年项目（30901835）：胎肾上腺CYP3A介导吡咯双环生物碱类发育毒性的代谢损伤机制; 中央高校基本科研业务费专项（2042017Kf1032）：吡咯里西啶生物碱致发育毒性的性别差异及其机制研究

Abstract

Abstract: Objective To explore the changes and causes of cholesterol level in fetal rats from cholestasis mother induced by monocrotaline (MCT) exposure. Methods Pregnant Wistar rats were treated with MCT(20 mg·kg-1·d-1) from gestation days (GDs) 11 to 20, and rats were sacrificed at GD 20. Maternal and fetal blood, placenta and fetal liver were collected. Cholesterol levels in maternal and fetal bloods were determined, and expression of placental cholesterol transporter and fetal liver cholesterol-related genes were examined. Results Compared with the control group, maternal blood bile acid and total cholesterol (TCH) levels were enhanced by MCT treatment. Male fetal blood TCH and low-density lipoprotein cholesterol (LDL-C) levels increased. Expression of low-density lipoprotein receptor (LDLR), scavenger receptor class B type I (SR-B1) and triphosphate binding cassette transporter A1 (ABCA1) were up-regulated in male and female fetal placentae from MCT group. In addition, expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), SR-B1, and LDLR were down-regulated in male and female fetal liver. Conclusion Maternal cholestasis induced by MCT exposure caused hypercholesterolemia in maternal and increased the expression of placental cholesterol transporter, leading to a high cholesterol level in fetal rats. Changes in the expression of cholesterol transporter in fetal liver suggest that MCT exposure during pregnancy may result in alteration of cholesterol homeostasis in fetal liver.

Key words: pregnancy, monocrotaline, intrahepatic cholestasis of pregnancy, cholesterol transport

CLC Number:

R961

GUO Qi, WANG Yanqing, CHENG Yanxiang, LIU Jie, QIU Shuaikai, XIANG E, WANG Hui, GUO Yu. ffects of Exposure to Monocrotaline on Cholesterol Levels of Fetal Rats[J]. Chinese Journal of Pharmacovigilance, 2019, 16(2): 71-75.

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ffects of Exposure to Monocrotaline on Cholesterol Levels of Fetal Rats

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