PMID- 28254502 OWN - NLM STAT- MEDLINE DCOM- 20180222 LR - 20211204 IS - 1618-1433 (Electronic) IS - 0940-2993 (Linking) VI - 69 IP - 6 DP - 2017 Jul 5 TI - Maternal exposure to titanium dioxide nanoparticles during pregnancy and lactation alters offspring hippocampal mRNA BAX and Bcl-2 levels, induces apoptosis and decreases neurogenesis. PG - 329-337 LID - S0940-2993(17)30106-9 [pii] LID - 10.1016/j.etp.2017.02.006 [doi] AB - INTRODUCTION: The usage of Titanium dioxide nanoparticles (TiO(2)-NPs) covers a vast area in different fields ranging from cosmetics and food to the production of drugs. Maternal exposure to TiO(2)-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(2)-NPs on rat offspring hippocampus during developmental period. MATERIAL AND METHODS: Pregnant and lactating Wistar rats received intragastric TiO(2)-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: Results of histopatological examination by TUNEL staining showed that maternal exposure to TiO(2)-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(2)-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(2)-NPs group significantly increased and decreased, respectively (P<0.01). CONCLUSION: These findings provide strong evidence that maternal exposure to TiO(2)-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. CI - Copyright (c) 2017 Elsevier GmbH. All rights reserved. FAU - Ebrahimzadeh Bideskan, Alireza AU - Ebrahimzadeh Bideskan A AD - Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. FAU - Mohammadipour, Abbas AU - Mohammadipour A AD - Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: MohammadiPA@mums.ac.ir. FAU - Fazel, Alireza AU - Fazel A AD - Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. FAU - Haghir, Hossein AU - Haghir H AD - Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Medical Genetic Research Center (MGRC), School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. FAU - Rafatpanah, Houshang AU - Rafatpanah H AD - Immunology Research Center, Buali Institute, Mashhad University of Medical Sciences, Mashhad, Iran. FAU - Hosseini, Mahmoud AU - Hosseini M AD - Neurocognitive Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. FAU - Rajabzadeh, Aliakbar AU - Rajabzadeh A AD - Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. LA - eng PT - Journal Article DEP - 20170227 PL - Germany TA - Exp Toxicol Pathol JT - Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie JID - 9208920 RN - 0 (Dcx protein, rat) RN - 0 (Doublecortin Protein) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (RNA, Messenger) RN - 0 (bcl-2-Associated X Protein) RN - 15FIX9V2JP (titanium dioxide) RN - D1JT611TNE (Titanium) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Doublecortin Protein MH - Female MH - Hippocampus/*drug effects/pathology MH - Lactation MH - Maternal Exposure/*adverse effects MH - Metal Nanoparticles/*toxicity MH - Neurogenesis/*drug effects MH - Pregnancy MH - Prenatal Exposure Delayed Effects/pathology MH - Proto-Oncogene Proteins c-bcl-2/biosynthesis/drug effects MH - RNA, Messenger/biosynthesis/drug effects MH - Rats MH - Rats, Wistar MH - Titanium/*toxicity MH - bcl-2-Associated X Protein/biosynthesis/drug effects OTO - NOTNLM OT - Apoptosis OT - Hippocampus OT - Maternal exposure OT - Neurogenesis OT - Titanium dioxide nanoparticles EDAT- 2017/03/04 06:00 MHDA- 2018/02/23 06:00 CRDT- 2017/03/04 06:00 PHST- 2016/07/24 00:00 [received] PHST- 2017/02/16 00:00 [revised] PHST- 2017/02/20 00:00 [accepted] PHST- 2017/03/04 06:00 [pubmed] PHST- 2018/02/23 06:00 [medline] PHST- 2017/03/04 06:00 [entrez] AID - S0940-2993(17)30106-9 [pii] AID - 10.1016/j.etp.2017.02.006 [doi] PST - ppublish SO - Exp Toxicol Pathol. 2017 Jul 5;69(6):329-337. doi: 10.1016/j.etp.2017.02.006. Epub 2017 Feb 27.