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

Rashid, Faizan; Ahmad, Saeed; Irudayaraj, Joseph

doi:10.3390/toxics8030064

Cited by 34 publications

(22 citation statements)

References 88 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…epithelia throughout the body including the blood-brain barrier (Burek et al 2019) and the epididymis (Dubé et al 2010). Notably, a recent study of PFOA exposure in mice reported changes in the expression of tight junction genes in the small intestine, with possible adverse impacts on gut barrier functions (Rashid et al 2020).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Prenatal Exposure to Per- and Polyfluoroalkyl Substances, Umbilical Cord Blood DNA Methylation, and Cardio-Metabolic Indicators in Newborns: The Healthy Start Study

Starling

Liu

Shen

et al. 2020

Environ Health Perspect

View full text Add to dashboard Cite

Background: Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent chemicals widely detected in women of reproductive age. Prenatal PFAS exposure is associated with adverse health outcomes in children. We hypothesized that DNA methylation changes may result from prenatal PFAS exposure and may be linked to offspring cardio-metabolic phenotype. Objectives: We estimated associations of prenatal PFAS with DNA methylation in umbilical cord blood. We evaluated associations of methylation at selected sites with neonatal cardio-metabolic indicators. Methods: Among 583 mother–infant pairs in a prospective cohort, five PFAS were quantified in maternal serum (median 27 wk of gestation). Umbilical cord blood DNA methylation was evaluated using the Illumina HumanMethylation450 array. Differentially methylated positions (DMPs) were evaluated at a false discovery rate and differentially methylated regions (DMRs) were identified using comb-p (Šidák-adjusted ). We estimated associations between methylation at candidate DMPs and DMR sites and the following outcomes: newborn weight, adiposity, and cord blood glucose, insulin, lipids, and leptin. Results: Maternal serum PFAS concentrations were below the median for females in the U.S. general population. Moderate to high pairwise correlations were observed between PFAS concentrations ( ). Methylation at one DMP (cg18587484), annotated to the gene TJAP1 , was associated with perfluorooctanoate (PFOA) at . Comb-p detected between 4 and 15 DMRs for each PFAS. Associated genes, some common across multiple PFAS, were implicated in growth ( RPTOR ), lipid homeostasis ( PON1 , PON3 , CIDEB , NR1H2 ), inflammation and immune activity ( RASL11B , RNF39 ), among other functions. There was suggestive evidence that two PFAS-associated loci (cg09093485, cg09637273) were associated with cord blood triglycerides and birth weight, respectively ( ). Discussion: DNA methylation in umbilical cord blood was associated with maternal serum PFAS concentrations during pregnancy, suggesting potential associations with offspring growth, metabolism, and immune function. Future research should explore whether DNA methylation changes mediate associations between prenatal PFAS exposures and child health outcomes. https://doi.org/10.1289/EHP6888

show abstract

Section: Discussionmentioning

confidence: 99%

“…2010 ). Notably, a recent study of PFOA exposure in mice reported changes in the expression of tight junction genes in the small intestine, with possible adverse impacts on gut barrier functions ( Rashid et al. 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Prenatal Exposure to Per- and Polyfluoroalkyl Substances, Umbilical Cord Blood DNA Methylation, and Cardio-Metabolic Indicators in Newborns: The Healthy Start Study

Starling

Liu

Shen

et al. 2020

Environ Health Perspect

View full text Add to dashboard Cite

show abstract

“…An increased incidence of UC has previously been reported in response to high exposure to PFOA through contaminated drinking water in mid-Ohio, United States (U.S) [7]. This observation is supported by findings from animal studies, where PFOA has been reported to alter the immune response and the barrier function via regulation of various cytokines and tight junction proteins [8].…”

Section: Introductionmentioning

confidence: 55%

“…Contamination of drinking water with high levels of PFOA, one of the most common PFAS, has also been associated with an increased incidence of UC in the state of Ohio, U.S. [7]. A recent study further showed that mice dosed with PFOA during 10 days displayed an altered expression of tight junction genes in the ileum compared to the colon [8]. These observations indicate that PFAS may play a role in the pathophysiology of IBD and potentially act as an environmental trigger.…”

Section: Discussionmentioning

confidence: 99%

Perfluoroalkyl Substances are increased in patients with Late-Onset Ulcerative colitis and induce Intestinal Barrier defects ex vivo in Murine Intestinal tissue

Fart

Salihović

McGlinchey

et al. 2020

Preprint

View full text Add to dashboard Cite

Background and aim: Environmental factors are strongly implicated in late-onset inflammatory bowel disease. By measuring perfluoroalkyl substances we investigate whether high exposure correlates with late-onset inflammatory bowel disease, and disturbances of the bile acid pool. We further explore the effect of perfluoronoctanoic acid on intestinal barrier function in murine tissue. Methods: Serum levels of perfluoroalkyl substances and bile acids were assessed in matched samples from patients with ulcerative colitis (n=20) and Crohn's disease (n=20) diagnosed at the age of ≥55 years. Blood donors (n=20), were used as healthy controls. The metabolites were assessed by ultra-performance liquid chromatography coupled to a triple-quadrupole mass spectrometer. Ex vivo exposure of perfluoronoctanoic acid in ileal and colonic murine tissue was assessed with the Ussing Chamber methodology (n=5). Results: The total amount of perfluoroalkyl substances was significantly increased in patients with ulcerative colitis compared to healthy controls or patients with Crohn's disease (p<0.05). Ex vivo exposure of 100 μM perfluoronoctanoic acid induced a significantly increased paracellular permeability across ileum (p<0.05) and an enhanced carbachol-induced ion secretion in colon. The distribution of bile acids as well as the correlation pattern between perfluoroalkyl substances and bile acids differed between patient groups and controls. Conclusion: Our results demonstrate that perfluoroalkyl substances levels are increased in patients with late-onset ulcerative colitis and might contribute to the disease by inducing a dysfunctional intestinal barrier or indirectly by interfering with the bile acid metabolism and thereby alter the intestinal barrier function.

show abstract

“…Ten-eleven translocation (TETs) family of enzymes play a crucial role in the demethylation, by catalyzing the hydroxylation of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC), 5-hmC to 5-formylcytosine (5-fC) and 5-fC to 5-carboxylcytosine (5-caC). Thus, DNA methyltransferases and Ten-eleven translocation enzymes play a coordinating role in modifying the epigenome [ 77 ]. Our results for gene expression analysis for DNMTs and TETs indicated decreased expression of DNMT1 and DNMT3b on exposure to higher doses (200- and 400 μM) of PFOA and PFOS, and increased expression of TET2 on PFOS exposure, and TET3 at higher doses (200- and 400 μM) of PFOA and PFOS.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Modifications, and Alterations in Cell Cycle and Apoptosis Pathway in A549 Lung Carcinoma Cell Line upon Exposure to Perfluoroalkyl Substances

Jabeen

Fayyaz

Irudayaraj

2020

Toxics

View full text Add to dashboard Cite

Per- and polyfluoroalkyl substances (PFAS) are a group of human-made compounds with strong C-F bonds, and have been used in various manufacturing industries for decades. PFAS have been reported to deleterious effect on human health, which has led to studies identifying the possible toxicity and toxicity routes of these compounds. We report that these compounds have the potential to cause epigenetic modifications, and to induce dysregulation in the cell proliferation cycle as well as apoptosis in A549 lung cancer cells when exposed to 10-, 200- and 400 μM concentrations of each compound. Our studies show that exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) may cause hypomethylation in the epigenome, but changes in the epigenetic makeup are not evident upon exposure to GenX. We establish that exposure to lower doses of these compounds causes the cells’ balance to shift to cell proliferation, whereas exposure to higher concentrations shifts the balance more towards apoptosis. Furthermore, the apoptosis pathway upon exposure to GenX, PFOA, and PFOS has also been identified. Our findings suggest that exposure to any of these compounds may have profound effects in patients with pre-existing lung conditions or could trigger lung cancinogenesis.

show abstract

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

Cited by 34 publications

References 88 publications

Prenatal Exposure to Per- and Polyfluoroalkyl Substances, Umbilical Cord Blood DNA Methylation, and Cardio-Metabolic Indicators in Newborns: The Healthy Start Study

Prenatal Exposure to Per- and Polyfluoroalkyl Substances, Umbilical Cord Blood DNA Methylation, and Cardio-Metabolic Indicators in Newborns: The Healthy Start Study

Perfluoroalkyl Substances are increased in patients with Late-Onset Ulcerative colitis and induce Intestinal Barrier defects ex vivo in Murine Intestinal tissue

Epigenetic Modifications, and Alterations in Cell Cycle and Apoptosis Pathway in A549 Lung Carcinoma Cell Line upon Exposure to Perfluoroalkyl Substances

Contact Info

Product

Resources

About