Prenatal Polycyclic Aromatic Hydrocarbon, Adiposity, Peroxisome Proliferator-Activated Receptor (PPAR) γ Methylation in Offspring, Grand-Offspring Mice

Abstract

RationaleGreater levels of prenatal exposure to polycyclic aromatic hydrocarbon (PAH) have been associated with childhood obesity in epidemiological studies. However, the underlying mechanisms are unclear.ObjectivesWe hypothesized that prenatal PAH over-exposure during gestation would lead to weight gain and increased fat mass in offspring and grand-offspring mice. Further, we hypothesized that altered adipose gene expression and DNA methylation in genes important to adipocyte differentiation would be affected.Materials and MethodsPregnant dams were exposed to a nebulized PAH mixture versus negative control aerosol 5 days a week, for 3 weeks. Body weight was recorded from postnatal day (PND) 21 through PND60. Body composition, adipose cell size, gene expression of peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/enhancer-binding proteins (C/EBP) α, cyclooxygenase (Cox)-2, fatty acid synthase (FAS) and adiponectin, and DNA methylation of PPAR γ, were assayed in both the offspring and grand-offspring adipose tissue.FindingsOffspring of dams exposed to greater PAH during gestation had increased weight, fat mass, as well as higher gene expression of PPAR γ, C/EBP α, Cox2, FAS and adiponectin and lower DNA methylation of PPAR γ. Similar differences in phenotype and DNA methylation extended through the grand-offspring mice.ConclusionsGreater prenatal PAH exposure was associated with increased weight, fat mass, adipose gene expression and epigenetic changes in progeny.

The Role of Epigenetics in the Latent Effects of Early Life Exposure to Obesogenic Endocrine Disrupting Chemicals

“…Perinatal airborne PAH exposure was related to the development of adiposity in the F1 and F2 generation, with persistent changes in body weight, fat mass, and adipocyte size. Expression of the genes encoding PPAR␥ and related adipogenic genes was increased and accompanied by decreased DNA methylation in the promoter of Ppar␥ (45). The authors of this study associate the obesogenic effects of the PAH mixture to direct activation of Ppar␥, although it is conceivable that other mechanisms are involved, given the multiple endocrine disrupting and carcinogenic properties of PAHs and their metabolites.…”

“…To our knowledge, one of the first studies to examine the effects of mixtures of EDCs on obesity-related outcomes and epigenetic gene regulation was recently published, in which pregnant dams were exposure to an airborne mixture of PAHs in aerosol form that was designed to replicate the proportions of individual PAH measured in pregnant women (45). Perinatal airborne PAH exposure was related to the development of adiposity in the F1 and F2 generation, with persistent changes in body weight, fat mass, and adipocyte size.…”

Impact of prenatal polycyclic aromatic hydrocarbon exposure on behavior, cortical gene expression, and DNA methylation of the Bdnf gene

“…The PAH mixture was produced by the Lovelace Respiratory Research Institute to replicate the proportions of individual PAH that was measured among a cohort of over 700 pregnant women using personal air sampling devices [18, 19, 27]. Briefly, the negative control aerosol solution consisted of 99.97% purified water, 0.02% Tween 80 and 0.01% antifoam (Sigma-Aldrich, St. Louis, MO).…”

“…In the current study, we conducted analyses of the impact of prenatal exposure to PAH on behavior, brain gene expression and DNA methylation in mice exposed to an aerosolized mixture that simulates the prenatal PAH exposure of a CCCEH cohort of children from Northern New York City [18, 19]. Within this study, we assessed behavioral outcomes related to cognition, activity levels, and anxiety-like phenotypes and focused on the expression of two candidate genes implicated in neural plasticity: brain derived neurotrophic factor ( Bdnf ) and the ionotropic glutamate receptor, N-methyl D-aspartate 2B ( Grin2b, or Nmdar2b ).…”

Polycyclic aromatic hydrocarbons are associated with insulin receptor substrate 2 methylation in adipose tissues of Korean women

“…PAH is also suggested to possess these properties (Irigaray et al, 2006). A previous study has shown that prenatal PAH exposure in mice has the potential to inappropriately stimulate adipogenesis and fat storage, influence metabolism and energy balance, and increase susceptibility to obesity (Yan et al, 2014).…”