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母体暴露于低剂量双酚 A 及其对雄性幼仔潜在神经毒性的影响:组织学、免疫组织化学和超微结构研究。

Maternal exposure to low-dose bisphenol A and its potential neurotoxic impact on male pups: A histological, immunohistochemical, and ultrastructural study.

机构信息

Human Anatomy and Embryology, Faculty of Medicine, Zagazig University, 44519, Egypt.

出版信息

Tissue Cell. 2024 Oct;90:102503. doi: 10.1016/j.tice.2024.102503. Epub 2024 Aug 3.

DOI:10.1016/j.tice.2024.102503
PMID:39137535
Abstract

BACKGROUND

Bisphenol A (BPA) is a widely used chemical with a harmful effect on animal and human. The neonatal and juvenile period is a highly risky neurodevelopmental period.

AIM

This study aimed to determine how male albino rat pups' cerebral cortex was altered by low doses of BPA given to mothers and the role of the oxidative stress.

METHODS

Thirty pregnant rats were randomly split into three equal groups, negative control, and positive control: received 1 cc of corn oil once a day through gastric tube and BPA treated: a dose of 200 µg/kg/day (dissolved in 1 cc corn oil). The male rat pups of each group were sacrificed at 1 week, 3 weeks and 6 weeks. The cerebra were then separated from the brain for histological and biochemical studies.

RESULTS

Rats administered BPA had raised levels of lipid peroxidation marker (MDA), lower levels of enzymatic antioxidants (SOD and CAT) with decreased body, cerebral weights, and decreased levels of non-enzymatic antioxidant defense (GSH). Histo-pathologically, shrunken pyramidal cells with congested blood vessels appeared. GFAP displayed increased number of positive immune-reactive astrocytes with high statistically significant increase in the area % in BPA treated group when compared to the control groups, on contrary to MBP. Semi-thin and ultra-thin BPA-sections revealed degenerative changes in myelinated axons with tiny nucleus and broken nuclear membranes. Lysosomes, dilated endoplasmic reticulum cisternae with noticeable increase in unmyelinated nerve fibers were also observed.

CONCLUSION

The structure of the developing cerebral cortex is negatively impacted by BPA due to oxidative stress.

摘要

背景

双酚 A(BPA)是一种广泛使用的化学物质,对动物和人类都有有害影响。新生儿和青少年时期是神经发育高度危险的时期。

目的

本研究旨在确定低剂量 BPA 对母体和氧化应激作用下雄性白化大鼠幼仔大脑皮质的影响。

方法

将 30 只怀孕大鼠随机分为三组,阴性对照组和阳性对照组每天通过胃管给予 1 cc 玉米油,BPA 处理组:给予 200 µg/kg/天的剂量(溶解在 1 cc 玉米油中)。每组雄性幼鼠在 1 周、3 周和 6 周时处死。然后将大脑从大脑中分离出来进行组织学和生化研究。

结果

给予 BPA 的大鼠脂质过氧化标志物(MDA)水平升高,酶抗氧化剂(SOD 和 CAT)水平降低,体重和脑重降低,非酶抗氧化防御水平(GSH)降低。组织病理学上,出现了萎缩的锥体细胞和充血的血管。GFAP 显示出更多的阳性免疫反应性星形胶质细胞,与对照组相比,BPA 处理组的阳性细胞面积百分比具有统计学意义的显著增加,而 MBP 则相反。半薄和超薄 BPA 切片显示髓鞘轴突变性改变,细胞核缩小,核膜破裂。溶酶体、内质网扩张的 cisterna 也可见,未髓鞘化神经纤维明显增加。

结论

由于氧化应激,BPA 对发育中大脑皮质的结构产生负面影响。

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