title: Maternal exposure to titanium dioxide nanoparticles during pregnancy and lactation alters offspring hippocampal mRNA BAX and Bcl-2 levels, induces apoptosis and decreases neurogenesis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Pregnant and lactating Wistar rats received intragastric TiO2-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 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Ebrahimzadeh Bideskan
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: MohammadiPA@mums.ac.ir.
authors.forename: Abbas
authors.initials: A
authors.lastname: Mohammadipour
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Fazel
authors.affiliation: 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.
authors.forename: Hossein
authors.initials: H
authors.lastname: Haghir
authors.affiliation: Immunology Research Center, Buali Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Houshang
authors.initials: H
authors.lastname: Rafatpanah
authors.affiliation: Neurocognitive Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Hosseini
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Aliakbar
authors.initials: A
authors.lastname: Rajabzadeh
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000089662:Doublecortin Protein; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D007774:Lactation; D018811:Maternal Exposure / Q000009:adverse effects*; D053768:Metal Nanoparticles / Q000633:toxicity*; D055495:Neurogenesis / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014025:Titanium / Q000633:toxicity*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000187:drug effects
chemical_list: C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; C009495:titanium dioxide; D014025:Titanium
keywords: Apoptosis; Hippocampus; Maternal exposure; Neurogenesis; Titanium dioxide nanoparticles