Prenatal air pollution exposure induces sexually dimorphic fetal programming of metabolic and neuroinflammatory outcomes in adult offspring

Brain Behav Immun. 2014 Mar;37:30-44. doi: 10.1016/j.bbi.2013.10.029. Epub 2013 Nov 1.

Abstract

Environmental chemical exposures during critical windows of development may contribute to the escalating prevalence of obesity. We tested the hypothesis that prenatal exposure to diesel exhaust particles (DEP), a primary component of air pollution, would prime microglia long-term, resulting in exacerbated metabolic and affective outcomes following exposure to a high-fat diet in adulthood. Time-mated mouse dams were intermittently exposed to respiratory instillations of either vehicle (VEH) or DEP throughout gestation. Adult male and female offspring were then fed either a low-fat diet (LFD) or high-fat diet (HFD) for 9 weeks. The male offspring of DEP-exposed dams exhibited exaggerated weight gain, insulin resistance, and anxiety-like behavior on HFD compared to the male offspring of VEH-exposed dams, whereas female offspring did not differ according to prenatal treatment. Furthermore, HFD induced evidence of macrophage infiltration of both adipose tissue and the brain in both sexes, but these cells were more activated specifically in DEP/HFD males. DEP/HFD males also expressed markedly higher levels of microglial/macrophage, but not astrocyte, activation markers in the hippocampus, whereas females exhibited only a suppression of astrocyte activation markers due to HFD. In a second experiment, DEP male offspring mounted an exaggerated peripheral IL-1β response to an LPS challenge at postnatal day (P)30, whereas their central IL-1β response did not differ from VEH male offspring, which is suggestive of macrophage priming due to prenatal DEP exposure. In sum, prenatal air pollution exposure "programs" offspring for increased susceptibility to diet-induced metabolic, behavioral, and neuroinflammatory changes in adulthood in a sexually dimorphic manner.

Keywords: Adipose tissue; Anxiety; Diesel exhaust particles; Fetal programming; High-fat diet; Hippocampus; Hypothalamus; Insulin resistance; Macrophages; Microglia.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Air Pollution*
  • Animals
  • Anxiety / chemically induced
  • CD11b Antigen / metabolism
  • CX3C Chemokine Receptor 1
  • Diet, High-Fat
  • Female
  • Fetus / metabolism*
  • Hippocampus / metabolism
  • Hypothalamus / metabolism
  • Inflammation
  • Insulin Resistance
  • Male
  • Maternal Behavior
  • Mice
  • Mice, Inbred C57BL
  • Pregnancy
  • Prenatal Exposure Delayed Effects / metabolism*
  • Prenatal Exposure Delayed Effects / psychology
  • Receptors, CCR2 / metabolism
  • Receptors, Chemokine / metabolism
  • Sex Factors
  • Toll-Like Receptor 4 / metabolism
  • Vehicle Emissions / toxicity*
  • Weight Gain

Substances

  • CD11b Antigen
  • CX3C Chemokine Receptor 1
  • Ccr2 protein, mouse
  • Cx3cr1 protein, mouse
  • Receptors, CCR2
  • Receptors, Chemokine
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Vehicle Emissions