Effect of Perfluorooctanoic Acid on the Epigenetic and Tight Junction Genes of the Mouse Intestine.

Faizan Rashid,Joseph Maria Kumar Irudayaraj,Saeed Ahmad

doi:10.3390/toxics8030064

Faizan Rashid, Joseph Maria Kumar Irudayaraj + Show 1 more

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https://doi.org/10.3390/toxics8030064

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Abstract

Perfluorooctanoic acid (PFOA) has been implicated in various toxicities including neurotoxicity, genotoxicity, nephrotoxicity, epigenetic toxicity, immunotoxicity, reproductive toxicity, and hepatotoxicity. However, information on the accumulation of PFOA in the intestine and its toxic effects on intestinal epigenetics and tight junction (TJ) genes is sparse. CD1 mice were dosed with PFOA (1, 5, 10, or 20 mg/kg/day) for 10 days, and its accumulation and induced alterations in the expression of epigenetic and tight junction genes in the small intestine and colon were evaluated using LC–MS and qPCR techniques. PFOA reduced the expression levels of DNA methyltransferases (Dnmt1, Dnmt3a, Dnmt3b) primarily in the small intestine whereas, in the colon, a decrease was observed only at high concentrations. Moreover, ten-eleven translocation genes (Tet2 and Tet3) expression was dysregulated in the small intestine, whereas in the colon Tets remained unaffected. The tight junction genes Claudins (Cldn), Occludin (Ocln), and Tight Junction Protein (Tjp) were also heavily altered in the small intestine. TJs responded differently across the gut, in proportion to PFOA dosing. Our study reveals that PFOA triggers DNA methylation changes and alters the expression of genes essential for maintaining the physical barrier of intestine, with more profound effects in the small intestine compared to the colon.

Highlights

Perfluorooctanoic acid (PFOA) is an eight-carbon chain (C8) compound which belongs to a group of synthetic chemicals known as perfluoroalkyl and polyfluoroalkyl substances (PFASs)
We examined the bioaccumulation of PFOA in the small intestine and colon tissues and the relative expression of (1) epigenetic effector genes, which are DNA methyltransferase (Dnmts) and ten–eleven translocation (Tets), and (2) intestinal tight junction (TJ) genes (i.e., occludin (Ocln), claudins (Cldns) and zonula occludens (ZOs)), which have a key role in the maintenance of physical barriers in the intestine
10 days of PFOA exposure, small intestine and colon tissues of the female CD1 mice were noted to PFOA, the persistent perfluoroalkyl substance, has a high potential to accumulate in human and have a significant amount of PFOA accumulation compared to the control group in which no PFOA

Summary

Introduction

Perfluorooctanoic acid (PFOA) is an eight-carbon chain (C8) compound which belongs to a group of synthetic chemicals known as perfluoroalkyl and polyfluoroalkyl substances (PFASs). Among PFASs, PFOA has been used excessively because of its polymerization properties in the synthesis of various fluoropolymers used in the production of commercial products, such as Gore-Tex and Teflon [3]. PFOA has been detected in house dust, [4] surface and drinking water, [5,6], indoor and outdoor air [7], and animal tissues [8,9]. Humans are exposed to PFOA through diet, primarily eggs, fish products, poultry products, cereals, vegetables and drinking water, inhalation of dust particles, and in commercial products [5,10,11,12]. PFOA has strong carbon–fluorine bonds which makes it a highly

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