Single and multiple sevoflurane exposures during pregnancy and offspring behavior in mice

Paediatr Anaesth. 2017 Jul;27(7):742-751. doi: 10.1111/pan.13139. Epub 2017 May 11.

Abstract

Background: The second trimester is a period of neurogenesis and neuronal migration, which can be affected by exposure to anesthetics. Studies also suggest that multiple exposures may have a greater impact on neurodevelopment.

Aim: We investigated whether in utero single or multiple exposures to anesthetics caused long-term behavior changes.

Methods: Pregnant mice were randomly divided into four groups on gestational day 14 (GD 14). Mice in the Control × 1 group were exposed to 100% oxygen for 150 min. Mice in the Sevo × 1 group were also exposed to 100% oxygen for 150 min, except that 2.5% sevoflurane was added during the first 120 min. Mice in the Control × 3 and Sevo × 3 group were identically treated as Control × 1 and Sevo × 1 group for three consecutive days, respectively (GD 14-16). Behavioral tests were performed only with the male offspring at the age of 2-4 months. Synaptic plasticity was also compared by inducing long-term potentiation in acute hippocampal slices.

Results: Single or multiple sevoflurane exposures in pregnant mice during the second trimester did not cause long-lasting behavioral consequences or changes in long-term synaptic plasticity of their offspring.

Conclusion: Our study suggests that neither single nor multiple exposures of mice to sevoflurane during the fetal developmental period induces long-term behavioral dysfunctions or affects long-term synaptic plasticity. Additional studies focusing on early stages of neurodevelopment are necessary to confirm the effects of sevoflurane exposure during pregnancy.

Keywords: anesthesia; fetus; neurodevelopmental disorders; sevoflurane.

MeSH terms

  • Anesthetics, Inhalation / toxicity*
  • Animals
  • Animals, Newborn
  • Anxiety / chemically induced
  • Anxiety / psychology
  • Behavior, Animal / drug effects*
  • Excitatory Postsynaptic Potentials / drug effects
  • Fear / drug effects
  • Female
  • Grooming / drug effects
  • Learning / drug effects
  • Long-Term Potentiation / drug effects
  • Memory / drug effects
  • Methyl Ethers / toxicity*
  • Mice
  • Mice, Inbred C57BL
  • Neuronal Plasticity / drug effects
  • Pregnancy
  • Prenatal Exposure Delayed Effects / psychology*
  • Sevoflurane
  • Social Behavior

Substances

  • Anesthetics, Inhalation
  • Methyl Ethers
  • Sevoflurane