Mixtures of per- and polyfluoroalkyl substances (PFAS) alter sperm methylation and long-term reprogramming of offspring liver and fat transcriptome

Environment International, Journal Year: 2024, Volume and Issue: 186, P. 108577 - 108577

Published: March 16, 2024

Male fertility has been declining worldwide especially in countries with high levels of endocrine disrupting chemicals (EDCs). Per- and polyfluorinated alkyl Substances (PFAS) have classified as EDCs linked to adverse male reproductive health. The mechanisms these associations their implications on offspring health remain unknown. aims the current study were assess effect PFAS mixtures sperm methylome transcriptional changes metabolic tissues (i.e., liver fat). C57BL/6 mice exposed a mixture (PFOS, PFOA, PFNA, PFHxS, Genx; 20 µg/L each) for 18-weeks or water control. Genome-wide methylation was assessed F0 epidydimal using reduced representation bisulfite sequencing (RRBS) Illumina mouse array, while gene expression by bulk RNA 8-week-old derived from unexposed females. resulted 2,861 83 (Illumina) DMRs (q < 0.05). Functional enrichment revealed that PFAS-induced associated behavior developmental pathways RRBS, related lipid metabolism cell signaling. Additionally, 40 53 differentially expressed genes (DEGs) fat males, 9 31 DEGs females, respectively. alterations cholesterol mitotic cycle regulation myeloid leukocyte migration offspring, female erythrocyte development carbohydrate catabolism affected fat. Our results demonstrate exposure legacy newly emerging adult result aberrant altered sex-specific manner. These data indicate preconception males can be transmitted affect phenotype next generation.

Language: Английский

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Kynurenic Acid Plays a Protective Role in Hepatotoxicity Induced by HFPO-DA in Male Mice

Environmental Science & Technology, Journal Year: 2024, Volume and Issue: 58(4), P. 1842 - 1853

Published: Jan. 16, 2024

Following its introduction as an alternative to perfluorooctanoic acid, hexafluoropropylene oxide dimer acid (HFPO-DA) has been extensively detected in various environmental matrices. Despite this prevalence, limited information is available regarding hepatotoxicity biomarkers. In study, toxicokinetic simulations indicated that under repeated treatment, HFPO-DA mice serum reached a steady state by the 4th day. To assess subacute hepatic effects and identify potential biomarkers, were administered orally at doses of 0, 0.1, 0.5, 2.5, 12.5, or 62.5 mg/kg/d for 7 d. Results revealed lowest observed adverse effect levels 0.5 hepatomegaly 2.5 injury. Serum metabolomics analysis identified 34, 58, 118 differential metabolites groups, respectively, compared control group. Based on weighted gene coexpression network analysis, eight hepatotoxicity-related identified; among them, kynurenic (KA) mouse exhibited highest correlation with liver Furthermore, liver-targeted demonstrated exposure induced metabolic migration kynurenine pathway from KA nicotinamide adenine dinucleotide, resulting activation endoplasmic reticulum stress nuclear factor kappa-B signaling pathway. Notably, pretreatment significantly attenuated injury mice, highlighting pivotal roles HFPO-DA.

Language: Английский

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Forever Chemicals, Per-and Polyfluoroalkyl Substances (PFAS), in Lubrication

Lubricants, Journal Year: 2024, Volume and Issue: 12(4), P. 114 - 114

Published: March 29, 2024

Per- and polyfluoroalkyl substances (PFAS), also known as forever chemicals, exhibit exceptional chemical stability resistance to environmental degradation thanks their strong C-F bonds nonpolar nature. However, widespread use persistence have a devastating impact on the environment. This review examines roles of PFAS in tribological applications, specifically lubricants lubricating systems. article focuses conventional advanced lubricants, including ionic liquids (ILs) modern automotive vehicles. The objective this paper is provide comprehensive overview adverse impacts whilst acknowledging outstanding performance surface coatings, composite materials, additives oils greases. pathways through which are introduced into environment via systems such seals O-rings identified, alongside subsequent dispersion routes interfaces across they interact. Furthermore, we examine toxicological implications exposure terrestrial aquatic life forms, plants, animals, humans, along with ecological consequences bioaccumulation biomagnification trophic levels ecosystems. ends potential remediation strategies for use, treatment technologies, biodegradation, recovery recycling methods, search more environmentally benign alternatives.

Language: Английский

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Effects of PFAS on human liver transporters: implications for health outcomes

Toxicological Sciences, Journal Year: 2024, Volume and Issue: 200(2), P. 213 - 227

Published: May 9, 2024

Abstract Per- and polyfluoroalkyl substances (PFAS) have become internationally recognized over the past three decades as persistent organic pollutants used in production of various consumer industrial goods. Research efforts continue to gauge risk that historically used, newly produced, PFAS may cause human health. Numerous studies report toxic effects on liver well increased serum cholesterol levels adults. A major concern with PFAS, also dubbed “forever chemicals,” is they accumulate kidney persist serum. The mechanisms responsible for their disposition excretion humans are poorly understood. better understanding interaction transporters, it pertains other xenobiotics, could provide mechanistic insight into health guide toward assessment compounds development. This review summarizes current state literature emerging relationships (eg, substrates, inhibitors, modulators gene expression) between specific hepatic transporters. adaptive toxicological responses hepatocytes reveal linkages pathologies epidemiological findings highlighted. evidence suggests our molecular landscape must improve determine impact expression function hepatocyte transporters play a key role or xenobiotic disposition. From here, we can assess what these changes documented outcomes.

Language: Английский

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In utero exposures to perfluoroalkyl substances and the human fetal liver metabolome in Scotland: a cross-sectional study

The Lancet Planetary Health, Journal Year: 2024, Volume and Issue: 8(1), P. e5 - e17

Published: Jan. 1, 2024

BackgroundPerfluoroalkyl and polyfluoroalkyl substances are classed as endocrine disrupting compounds but continue to be used in many products such firefighting foams, flame retardants, utensil coatings, waterproofing of food packaging. Perfluoroalkyl exposure aberrantly modulates lipid, metabolite, bile acid levels, increasing susceptibility onset severity metabolic diseases, diabetes dysfunction-associated steatotic liver disease. To date, most studies humans have focused on perfluoroalkyl-exposure effects adults. In this study we aimed show if perfluoroalkyls present the human fetal they consequences for fetus.MethodsIn cross-sectional study, livers from elective termination pregnancies at Aberdeen Pregnancy Counselling Service, Aberdeen, UK, were analysed by both targeted (bile acids perfluoroalkyl substances) combined untargeted (lipids polar metabolites) mass spectrometry based metabolomic analyses, well with RNA-Seq. Only fetuses normally progressing (determined ultrasound scan before termination), terminated non-medical reasons, women older than 16 years, fluent English, between 11 21 weeks gestation collected. Women exhibiting considerable emotional distress or whose had anomalies identified excluded. Stringent bioinformatic statistical methods partial correlation network analysis, linear regression, pathway analysis applied data investigate association hepatic pathways.FindingsFetuses included collected Dec 2, 2004, Oct 27, 2014. 78 study: all metabolomics (40 female 38 male) 57 RNA-Seq (28 29 male). Metabolites associated these varied gestational age. Conjugated markedly positively 23 amino acids, fatty sugar derivatives inversely exposure, glycolithocholic was quantified perfluoroalkyl. Furthermore, 7α-hydroxy-4-cholesten-3-one, a marker synthesis rate, strongly levels detectable early week 12.InterpretationOur shows direct evidence utero specific key products. Our results provide that potential future consequences, manifests fetus first trimester gestation. profiles changes resemble those observed perinatal exposures. Such exposures already linked susceptibility, initiation, progression, exacerbation wide range diseases.FundingUK Medical Research Council, Horizon Europe Program European Union, Seventh Framework Programme NHS Grampian Endowments grants, Partnership Assessment Risks Chemicals, Swedish Formas, Novo Nordisk Foundation, Academy Finland.

Language: Английский

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