Intergenerational Effect of Early Life Exposure to Permethrin: Changes in Global DNA Methylation and in Nurr1 Gene Expression

Abstract

Environmental exposure to pesticides during the early stages of development represents an important risk factor for the onset of neurodegenerative diseases in adult age. Neonatal exposure to Permethrin (PERM), a member of the family of synthetic pyrethroids, can induce a Parkinson-like disease and cause some alterations in striatum of rats, involving both genetic and epigenetic pathways. Through gene expression analysis and global DNA methylation assessment in both PERM-treated parents and their untreated offspring, we investigated on the prospective intergenerational effect of this pesticide. Thirty-three percent of progeny presents the same Nurr1 alteration as rats exposed to permethrin in early life. A decrease in global genome-wide DNA methylation was measured in mothers exposed in early life to permethrin as well as in their offspring, whereas untreated rats have a hypermethylated genomic DNA. Further studies are however needed to elucidate the molecular mechanisms, but, despite this, an intergenerational PERM-induced damage on progenies has been identified for the first time.

Keywords: Nurr1; global DNA methylation; intergenerational effect; permethrin.

Figure 1

qPCR to quantify relative changes in Nurr1 expression in striatum of young rats exposed to permethrin treatment in early life. All expression values were normalized to the value of β-actin gene used as an internal control. * p < 0.05 vs. control.

Figure 2

qPCR to quantify Nurr1 expression relative changes in striatum of control, early life treated mother and offspring (F1 generation, untreated rats). All expression values were normalized to the value of β-actin gene used as an internal control. * p < 0.05; ** p< 0.01; *** p < 0.001 vs. matched sex control group.

Figure 3

Methylation sensitive Arbitrarily Primed PCR of four representative samples. UTM = Untreated Male; TM1 = Early life treated mother; S4M = Male F1 Offspring; S5F = Female F1 Offspring. M= Mono-digested DNA; D= Double-digested DNA. Arrows in yellow indicate the disappearing/appearing of bands; arrows in green indicate attenuation/intensification of bands.