Intrauterine inflammation induces sex-specific effects on neuroinflammation, white matter, and behavior

Brain Behav Immun. 2017 Nov;66:277-288. doi: 10.1016/j.bbi.2017.07.016. Epub 2017 Jul 21.

Abstract

Exposure to inflammation during pregnancy has been linked to adverse neurodevelopmental consequences for the offspring. One common route through which a developing fetus is exposed to inflammation is with intrauterine inflammation. To that end, we utilized an animal model of intrauterine inflammation (IUI; intrauterine lipopolysaccharide (LPS) administration, 50µg, E15) to assess placental and fetal brain inflammatory responses, white matter integrity, anxiety-related behaviors (elevated zero maze, light dark box, open field), microglial counts, and the CNS cytokine response to an acute injection of LPS in both males and females. These studies revealed that for multiple endpoints (fetal brain cytokine levels, cytokine response to adult LPS challenge) male IUI offspring were uniquely affected by intrauterine inflammation, while for other endpoints (behavior, microglial number) both sexes were similarly affected. These data advance our understanding of sex-specific effects of early life exposure to inflammation in a translationally- relevant model.

Keywords: Anxiety; Cytokine; Locomotor; Placenta; Prefrontal cortex; Prenatal inflammation; Sex difference; White matter.

MeSH terms

  • Animals
  • Behavior, Animal
  • Brain / embryology
  • Brain / metabolism*
  • Brain / pathology
  • Disease Models, Animal
  • Encephalitis / etiology
  • Encephalitis / genetics
  • Encephalitis / metabolism*
  • Female
  • Inflammation / chemically induced
  • Inflammation / complications*
  • Lipopolysaccharides / administration & dosage
  • Mice
  • Placenta / metabolism
  • Pregnancy
  • Pregnancy Complications / chemically induced
  • Pregnancy Complications / metabolism*
  • Sex Characteristics*
  • Uterine Diseases / chemically induced
  • Uterine Diseases / complications*
  • Uterine Diseases / metabolism*
  • White Matter / pathology*

Substances

  • Lipopolysaccharides