Early life exposure to di(2-ethylhexyl)phthalate causes age-related declines associated with insulin/IGF-1-like signaling pathway and SKN-1 in Caenorhabditis elegans
Journal
Environmental Pollution
Journal Volume
251
Pages
871-878
Date Issued
2019
Author(s)
Abstract
Di(2-ethylhexyl)phthalate (DEHP) is an ubiquitous and emerging contaminant that is widely present in food, agricultural crop, and the environment, posing a potential risk to human health. This study utilized the nematode Caenorhabditis elegans to decipher the toxic effects of early life exposure to DEHP on aging and its underlying mechanisms. The results showed that exposure to DEHP at 0.1 and 1.5 mg/L inhibited locomotive behaviors. In addition, DEHP exposure significantly shortened the mean lifespan of the worms and further adversely affected pharyngeal pumping rate and defecation cycle in aged worms. Moreover, DEHP exposure also further enhanced accumulation of age-related biomarkers including lipofuscin, lipid peroxidation, and intracellular reactive oxygen species in aged worms. In addition, exposure to DEHP significantly suppressed gene expression of hsp-16.1, hsp-16.49, and hsp-70 in aged worms. Further evidences showed that mutation of genes involved in insulin/IGF-1-like signaling (IIS) pathway (daf-2, age-1, pdk-1, akt-1, akt-2, and daf-16) restored lipid peroxidation accumulation upon DEHP exposure in aged worms, whereas skn-1 mutation resulted in enhanced lipid peroxidation accumulation. Therefore, IIS and SKN-1 may serve as an important molecular basis for DEHP-induced age-related declines in C. elegans. Since IIS and SKN-1 are highly conserved among species, the age-related declines caused by DEHP exposure may not be exclusive in C. elegans, leading to adverse human health consequences due to widespread and persistent DEHP contamination in the environment. Early life DEHP exposure causes age-related declines, leading to potential adverse human health consequences. ? 2019
SDGs
Other Subjects
Crops; Esters; Gene expression; Health; Health risks; Insulin; Lipids; Oxidation; Oxidative stress; Age-related; Agricultural crops; Caenorhabditis elegans; DEHP; Di-2-ethylhexyl phthalate; Emerging contaminant; Reactive oxygen species; SKN-1; Chemical contamination; insulin; lipofuscin; phthalic acid bis(2 ethylhexyl) ester; reactive oxygen metabolite; somatomedin C; akt-2 protein, C elegans; biological marker; Caenorhabditis elegans protein; DNA binding protein; heat shock protein; hsp-16.1 protein, C elegans; insulin; lipofuscin; phthalic acid bis(2 ethylhexyl) ester; plasticizer; protein kinase B; reactive oxygen metabolite; skn-1 protein, C elegans; somatomedin C; transcription factor; aging; bioaccumulation; biomarker; gene expression; hormone; mutation; nematode; phthalate; population decline; reactive oxygen species; signaling; toxicity; age 1 gene; aged; aging; akt 1 gene; akt 2 gene; animal experiment; Article; bioaccumulation; Caenorhabditis elegans; controlled study; daf 16 gene; daf 2 gene; defecation; environmental exposure; gene; gene expression; gene mutation; hsp 16.1 gene; hsp 16.49 gene; hsp 70 gene; lifespan; lipid peroxidation; locomotion; nonhuman; pdk 1 gene; signal transduction; skn 1 gene; aging; animal; biosynthesis; drug effect; genetics; longevity; metabolism; pollutant; signal transduction; toxicity; Caenorhabditis elegans; Aging; Animals; Biomarkers; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Diethylhexyl Phthalate; DNA-Binding Proteins; Environmental Pollutants; Heat-Shock Proteins; Insulin; Insulin-Like Growth Factor I; Lipid Peroxidation; Lipofuscin; Longevity; Plasticizers; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Signal Transduction; Transcription Factors
Publisher
Elsevier Ltd
Type
journal article