Ebrahimzadeh Bideskan Alireza, Mohammadipour Abbas, Fazel Alireza, Haghir Hossein, Rafatpanah Houshang, Hosseini Mahmoud, Rajabzadeh Aliakbar
Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Exp Toxicol Pathol. 2017 Jul 5;69(6):329-337. doi: 10.1016/j.etp.2017.02.006. Epub 2017 Feb 27.
The usage of Titanium dioxide nanoparticles (TiO-NPs) covers a vast area in different fields ranging from cosmetics and food to the production of drugs. Maternal exposure to TiO-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 TiO-NPs on rat offspring hippocampus during developmental period.
Pregnant and lactating Wistar rats received intragastric TiO-NPs (100mg/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 of histopatological examination by TUNEL staining showed that maternal exposure to TiO-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 TiO-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 TiO-NPs group significantly increased and decreased, respectively (P<0.01).
These findings provide strong evidence that maternal exposure to TiO-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.
二氧化钛纳米颗粒(TiO-NPs)的用途广泛,涵盖从化妆品、食品到药物生产等不同领域。孕期母体暴露于TiO-NPs与子代海马体损伤以及学习和记忆能力下降有关。然而,其损伤机制尚不清楚。本文描述了TiO-NPs在发育期间对大鼠子代海马体的体内神经毒性作用。
怀孕和哺乳期的Wistar大鼠分别在妊娠第2天(GD2)至第21天以及出生后第2天(PD2)至第21天每天接受胃内注射TiO-NPs(100mg/kg体重)。对照组动物通过灌胃给予等量的蒸馏水。在治疗过程结束时,将子代深度麻醉并处死。然后收集每组动物的大脑,对大鼠子代大脑切片进行TUNEL染色(用于检测凋亡细胞)和免疫染色(用于神经发生)。此外,从右半球取出右侧海马体(每组n = 6)用于评估Bax和Bcl-2水平的表达。
TUNEL染色的组织病理学检查结果显示,孕期和哺乳期母体暴露于TiO-NPs会使子代海马体中的凋亡细胞显著增加(P<0.01)。作为神经发生标志物的双皮质素(DCX)蛋白的免疫标记也显示,TiO-NPs会减少子代海马体中的神经发生(P<0.05)。此外,与对照组相比,TiO-NPs组中Bax和Bcl-2的mRNA水平分别显著升高和降低(P<0.01)。
这些发现提供了有力证据,表明孕期母体暴露于TiO-NPs会显著影响子代海马体的神经发生和凋亡。纳米颗粒暴露对全球数百万孕妇及其子代的潜在影响可能是毁灭性的。