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槲皮素对怀孕Wistar大鼠暴露于原油蒸汽所产生的胎儿发育及先天性骨骼异常的保护作用。

Protective effect of quercetin on fetal development and congenital skeletal anomalies against exposure of pregnant Wistar rats to crude oil vapor.

作者信息

Hussein Haifa Ali, Khazaeel Kaveh, Ranjbar Reza, Tabandeh Mohammad Reza, Alahmed Jala Amir Salman

机构信息

Department of Basic Sciences, Division of Anatomy and Embryology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran.

Stem Cells and Transgenic Technology Research Center (STTRC), Shahid Chamran University of Ahvaz, Ahvaz, Iran.

出版信息

Birth Defects Res. 2023 Oct 15;115(17):1619-1629. doi: 10.1002/bdr2.2240. Epub 2023 Aug 19.

Abstract

BACKGROUND

Epidemiological evidence indicates a relationship between maternal exposure to crude oil vapors (COV) during pregnancy and adverse pregnancy outcomes. Quercetin (QUE) is a plant flavonoid with purported antioxidant and anti-inflammatory effects, which has been shown to prevent birth defects. This study was aimed to investigate the protective role of QUE on fetal development and congenital skeletal anomalies caused by exposure of pregnant rats to COV.

METHODS

Twenty-four pregnant Wistar rats were randomly categorized into four groups of control, COV, COV + QUE, and QUE (50 mg/kg). The inhalation method was used to expose pregnant rats to COV from day 0 to 20 of pregnancy, and QUE was administered orally during this period. On day 20 of gestation, the animals were anesthetized and a laparotomy was performed, and then the weight and crown rump length (CRL) of the fetuses were determined. Skeletal stereomicroscopic evaluations of fetuses were performed using Alcian blue/Alizarin red staining method, and the expression of osteogenesis-related genes (Runx2 and BMP-4) was evaluated using qPCR.

RESULTS

This study showed that prenatal exposure to COV significantly reduced fetal weight and CRL, and expression of Runx2 and BMP-4 genes. Moreover, COV significantly increased the incidence of congenital skeletal anomalies such as cleft palate, spina bifida and non-ossification of the fetal bones. However, administration of QUE with exposure to COV improved fetal bone development and reduced congenital skeletal anomalies.

CONCLUSION

QUE can ameliorate the teratogenic effects of prenatal exposure to COV by increasing the expression of osteogenesis-related genes.

摘要

背景

流行病学证据表明,孕期母亲接触原油蒸汽(COV)与不良妊娠结局之间存在关联。槲皮素(QUE)是一种具有抗氧化和抗炎作用的植物类黄酮,已被证明可预防出生缺陷。本研究旨在探讨QUE对孕鼠暴露于COV所导致的胎儿发育及先天性骨骼异常的保护作用。

方法

将24只怀孕的Wistar大鼠随机分为四组:对照组、COV组、COV + QUE组和QUE组(50 mg/kg)。采用吸入法使孕鼠在妊娠第0天至第20天暴露于COV,在此期间口服QUE。在妊娠第20天,将动物麻醉并进行剖腹手术,然后测定胎儿的体重和顶臀长度(CRL)。采用阿尔新蓝/茜素红染色法对胎儿进行骨骼立体显微镜评估,并使用qPCR评估成骨相关基因(Runx2和BMP-4)的表达。

结果

本研究表明,产前暴露于COV会显著降低胎儿体重、CRL以及Runx2和BMP-4基因的表达。此外,COV显著增加了先天性骨骼异常的发生率,如腭裂、脊柱裂和胎儿骨骼未骨化。然而,在暴露于COV的同时给予QUE可改善胎儿骨骼发育并减少先天性骨骼异常。

结论

QUE可通过增加成骨相关基因的表达来改善产前暴露于COV的致畸作用。

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