Chlorpyrifos-induced toxicity has no gender selectivity in the early fetal brain

J Environ Sci Health B. 2020;55(9):803-812. doi: 10.1080/03601234.2020.1786326. Epub 2020 Jun 30.

Abstract

Organophosphorus pesticides induce gender-specific developmental neurotoxicity after birth, especially in adolescents and adults. However, whether and when the selectivity occurs in fetus remains unclear. In this study, we analyzed chlorpyrifos (CPF)-induced neurotoxicity in the early fetal brains of male and female mice. The gestational dams were administered 0, 1, 3, and 5 mg/(kg.d) CPF during gestational days (GD)7-11, and brains from the fetuses were isolated and analyzed on GD12. Fetal gender was identified by PCR technique based on male-specific Sry gene and Myog control gene. The body weight and head weight, the activity of acetylcholinesterase (AChE), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and the content of malondialdehyde (MDA), as well as the oxidative stress-related gene expression were examined. Our results showed that CPF pretreatment induced AChE inhibition in GD12 fetal brain. CPF treatment activated SOD and GPX but not CAT and MDA. For oxidative stress-related gene expression, CPF pretreatment increased mRNA expression of Sod1, Cat, Gpx1, and Gpx2 in the fetal brain on GD12. The statistical analysis did not show gender-selective CPF-induced toxicity. Moreover, our results showed that although the gestational exposure to CPF could elicit abnormalities in the early fetal brain, the toxicity observed was not gender-specific.

Keywords: Organophosphorus pesticides; developmental neurotoxicity; early neurogenesis; gender selectivity.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • Body Weight / drug effects
  • Brain / drug effects*
  • Brain / embryology*
  • Brain / metabolism
  • Catalase / genetics
  • Catalase / metabolism
  • Chlorpyrifos / toxicity*
  • Cholinesterase Inhibitors / toxicity
  • Female
  • Gene Expression Regulation, Developmental / drug effects
  • Insecticides / toxicity*
  • Male
  • Malondialdehyde / metabolism
  • Mice, Inbred ICR
  • Neurotoxicity Syndromes / etiology
  • Organ Size / drug effects
  • Oxidative Stress / drug effects
  • Oxidative Stress / genetics
  • Sex Factors
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Toxicity Tests / methods

Substances

  • Cholinesterase Inhibitors
  • Insecticides
  • Malondialdehyde
  • Catalase
  • Superoxide Dismutase
  • Acetylcholinesterase
  • Chlorpyrifos