Maternal exposure to titanium dioxide nanoparticles during pregnancy and lactation alters offspring hippocampal mRNA BAX and Bcl-2 levels, induces apoptosis and decreases neurogenesis

Q2 Medicine

Experimental and Toxicologic Pathology Pub Date : 2017-07-05 DOI:10.1016/j.etp.2017.02.006

Alireza Ebrahimzadeh Bideskan , Abbas Mohammadipour , Alireza Fazel , Hossein Haghir , Houshang Rafatpanah , Mahmoud Hosseini , Aliakbar Rajabzadeh

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引用次数: 40

Abstract

Introduction

The usage of Titanium dioxide nanoparticles (TiO₂-NPs) covers a vast area in different fields ranging from cosmetics and food to the production of drugs. Maternal exposure to TiO₂-NPs during developmental period has been associated with hippocampal injury and with a decrease in learning and memory status of the offspring. However, little is known about its injury mechanism. This paper describes the in vivo neurotoxic effects of TiO₂-NPs on rat offspring hippocampus during developmental period.

Material and methods

Pregnant and lactating Wistar rats received intragastric TiO₂-NPs (100 mg/kg body weight) daily from gestational day (GD) 2 to (GD) 21 and postnatal day (PD) 2 to (PD) 21 respectively. Animals in the control groups received an equal volume of distilled water via gavage.

At the end of the treatment process, offspring were deeply anesthetized and sacrificed. Then brains of each group were collected and sections of the rat offspring’s brains were stained using TUNEL staining (for detection of apoptotic cells) and immunostaining (for neurogenesis). Moreover, the right hippocampus (n = 6 per each group) were removed from the right hemisphere for evaluating the expression of Bax and Bcl-2 level.

Results

Results of histopatological examination by TUNEL staining showed that maternal exposure to TiO₂-NPs during pregnancy and lactation periods increased apoptotic cells significantly (P < 0.01) in the offspring hippocampus. The immunolabeling of double cortin (DCX) protein as neurogenesis marker also showed that TiO₂-NPs reduced neurogenesis in the hippocampus of the offspring (P < 0.05). Moreover, in comparison with the control group, the mRNA levels of Bax and Bcl-2 in the TiO₂-NPs group significantly increased and decreased, respectively (P < 0.01).

Conclusion

These findings provide strong evidence that maternal exposure to TiO₂-NPs significantly impact hippocampal neurogenesis and apoptosis in the offspring. The potential impact of nanoparticle exposure for millions of pregnant mothers and their offspring across the world is potentially devastating.

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母亲在怀孕和哺乳期间暴露于二氧化钛纳米颗粒会改变子代海马mRNA BAX和Bcl-2水平，诱导细胞凋亡并减少神经发生

二氧化钛纳米颗粒(TiO2-NPs)的应用范围广泛，从化妆品、食品到药品生产。母体在发育期间暴露于TiO2-NPs与海马损伤和后代学习和记忆状态下降有关。然而，对其损伤机制知之甚少。本文研究了TiO2-NPs对大鼠子代海马的体内神经毒性作用。材料与方法妊娠期和哺乳期Wistar大鼠在妊娠第2天至第21天和出生后第2天至第21天分别每日灌胃TiO2-NPs (100 mg/kg体重)。对照组给予等量蒸馏水灌胃。在治疗过程结束时，对幼鼠进行深度麻醉并处死。然后收集各组大鼠后代的脑组织，用TUNEL染色(检测凋亡细胞)和免疫染色(检测神经发生)对其脑组织切片进行染色。此外，从右半球取出右侧海马(每组n = 6)，评估Bax和Bcl-2的表达水平。结果TUNEL染色组织病理学检查结果显示，母体在妊娠期和哺乳期暴露于TiO2-NPs中，凋亡细胞明显增加(P <0.01)。双皮质素(DCX)蛋白作为神经发生标志物的免疫标记也表明，TiO2-NPs减少了后代海马的神经发生(P <0.05)。此外，与对照组相比，TiO2-NPs组Bax和Bcl-2 mRNA水平分别显著升高和降低(P <0.01)。结论母体暴露于TiO2-NPs对后代海马神经发生和凋亡有显著影响。纳米颗粒暴露对全世界数百万孕妇及其后代的潜在影响可能是毁灭性的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental and Toxicologic Pathology 医学-病理学

CiteScore

2.08

自引率

0.00%

发文量

审稿时长

5.3 weeks

期刊介绍： Cessation. The international multidisciplinary journal is devoted to the publication of studies covering the whole range of experimental research on disease processes and toxicology including cell biological investigations. Its aim is to support progress in the interdisciplinary cooperation of researchers working in pathobiology, toxicology, and cell biology independent of the methods applied. During the past decades increasing attention has been paid to the importance of toxic influence in the pathogenesis of human and animal diseases. This is why Experimental and Toxicologic Pathology meets the urgent need for an interdisciplinary journal felt by a wide variety of experts in medicine and biology, including pathologists, toxicologists, biologists, physicians, veterinary surgeons, pharmacists, and pharmacologists working in academic, industrial or clinical institutions.