Maternal exposure to titanium dioxide nanoparticles during pregnancy; impaired memory and decreased hippocampal cell proliferation in rat offspring

Environ Toxicol Pharmacol. 2014 Mar;37(2):617-25. doi: 10.1016/j.etap.2014.01.014. Epub 2014 Jan 30.


Titanium dioxide nanoparticles (TiO2-NPs) are massively produced in the environment, and because of their wide usage, they are a potential risk of damage to human health. TiO2-NPs are often used as additives for paints, papers, and foods. The central nervous system (CNS), including hippocampal regions, is potentially susceptible targets for TiO2-NPs. This study aimed to determine the effects of exposure to TiO2-NPs during pregnancy on hippocampal cell proliferation and the learning and memory of offspring. Pregnant Wistar rats received intragastric TiO2-NPs (100 mg/kg body weight) daily from gestational day (GD) 2 to (GD) 21. Animals in the control group received the same volume of distilled water via gavage. After delivery, the one-day-old neonates were deeply anesthetized and weighed. They were then killed and the brains of each group were collected. Sections of the brains from the rat offspring were stained using Ki-67 immunolabeling and the immunohistochemistry technique. Some of the male offspring (n=12 for each group) were weaned at postnatal day (PND21), and housed until adulthood (PND60). Then the learning and memory in animals of each group were evaluated using passive avoidance and Morris water maze tests. The immunolabeling of Ki-67 protein as a proliferating cell marker showed that TiO2-NPs significantly reduced cell proliferation in the hippocampus of the offspring (P<0.05). Moreover, both the Morris water maze test and the passive avoidance test showed that exposure to TiO2-NPs significantly impaired learning and memory in offspring (P<0.05). These results may provide basic experimental evidence for a better understanding of the neurotoxic effects of TiO2-NPs on neonatal and adult brains.

Keywords: Hippocampal cell proliferation; Learning and memory; Maternal exposure; Neurotoxicity; Titanium dioxide nanoparticles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avoidance Learning / drug effects
  • Cell Proliferation / drug effects
  • Female
  • Hippocampus / cytology
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Maternal-Fetal Exchange
  • Maze Learning / drug effects
  • Memory / drug effects*
  • Metal Nanoparticles / toxicity*
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Rats, Wistar
  • Titanium / pharmacokinetics
  • Titanium / toxicity*


  • titanium dioxide
  • Titanium