Perfluorooctanoic Acid Treatment Research Articles

Novel insights on ecological responses of short- and long-chain perfluorocarboxylic acids in constructed wetlands coupled with modified basalt fiber bio-nest

The first investigation based on constructed wetlands coupled with modified basalt fiber bio-nest (MBF-CWs) was performed under exposure of short- and long-chain perfluorocarboxylic acids (PFCAs). In general, both perfluorooctanoic acid (PFOA) and perfluorobutanoic acid (PFBA) caused significant decline of chemical oxygen demand removal by 10.83 % and 4.73 %. However, only PFOA led to marked inhibition on total phosphorus removal by 12.51 % in whole duration. Suppression of removal performance resulted from side impacts on microbes by PFOA. For instance, activities of key enzymes like dehydrogenase (DHA), urease (URE), and phosphatase (PST) decreased by 52.77 %, 40.70 %, and 56.94 % in maximum under PFOA stress, while URE could alleviate over time. By contrast, distinct inhibition was only found on PST in later phases with PFBA exposure. PFCAs had adverse influence on alpha diversity of MBF-CWs, particularly long-chain PFOA. Both PFCAs caused enrichment of Proteobacteria, owing to increase of Gammaproteobacteria and Plasticicumulans by 22.04–35.79 % and 22.91–219.77 %. Nevertheless, some dominant phyla (like Bacteroidota and Acidobacteriota) and genera (like SC-I-84, Thauera, Subgroup_10, and Ellin6067) were only suppressed by PFOA, causing more hazards to microbial decontamination than PFBA did. As for plants, chlorophyll contents tend to decrease with PFOA treatment. Whereas, higher antioxidase activities and more lipid peroxidation products were uncovered in PFOA group, demonstrating more reactive oxygen species brought by long-chain PFCAs. This work offered new findings about ecological effects of MBF-CWs under PFCAs exposure, evaluating stability and sustainability of MBF-CW systems to treat sewage containing complex PFCAs.

Physiological impact of perfluorooctanoic acid (PFOA) on the cyanobacterium Microcystis aeruginosa

ABSTRACT Perfluorooctanoic acid (PFOA) is a surfactant that is detected in small quantities across various environments away from its manufacturing zones. Despite the widespread detection of PFOA in aquatic ecosystems, the impact of this compound on phytoplankton populations remains poorly understood. This study aimed to determine the physiological effects of PFOA on Microcystis aeruginosa. The cyanobacterium was exposed to 1‒10 000 μg l‒1 PFOA for 7 days under controlled laboratory conditions. The EC50 of PFOA for the test species after 7 days of exposure was 30.03 μg l‒1. Cell density significantly decreased at all PFOA concentrations (1‒10 000 μg l‒1). Chlorophyll a and carotenoid concentrations increased on day 1 (except for 1 μg l‒1, the lowest PFOA treatment) but then decreased across all treatment concentrations on day 7 of the experiment. When M. aeruginosa was exposed to PFOA, the total lipid, protein and carbohydrate content generally increased across all treatment concentrations. The concentration of intracellular hydrogen peroxide increased with increasing surfactant concentrations. In different treatments, lipid peroxidation increased, with 100 μg l‒1 PFOA producing the highest malondialdehyde content. Peroxidase and glutathione S-transferase activities increased across all treatment concentrations, demonstrating progressive changes consistent with the increase in reactive oxygen species observed. Total microcystin concentration increased in cultures exposed to 1000 and 10 000 µg l‒1 PFOA. These findings suggest that PFOA can adversely affect the survival of M. aeruginosa populations in contaminated aquatic ecosystems, with potential cascading effects on the general health of the environment.

Perfluorooctanoic acid-contaminated wastewater treatment by forward osmosis: Performance analysis

Perfluorooctanoic acid (PFOA) is a persistent compound, raising considerable global apprehension due to its resistance to breakdown and detrimental impacts on human health and aquatic environments. Pressure-driven membrane technologies treating PFAS-contaminated water are expensive and prone to fouling. This study presented a parametric investigation of the effectiveness of cellulose triacetate membrane in the forward osmosis (FO) membrane for removing PFOA from an aqueous solution. The study examined the influence of membrane orientation modes, feed pH, draw solution composition and concentration, and PFOA concentration on the performance of FO. The experimental results demonstrated that PFOA rejection was 99 % with MgCl2 and slightly >98 % with NaCl draw solutions due to the mechanism of PFOA binding to the membrane surface through Mg2+ ions. This finding highlights the crucial role of the draw solution's composition in PFOA treatment. Laboratory results revealed that membrane rejection of PFOA was 99 % at neutral and acidic pH levels but decreased to 95 % in an alkaline solution at pH 9. The decrease in membrane rejection is attributed to the dissociation of the membrane's functional groups, consequently causing pore swelling. The results were confirmed by calculating the average pore radius of the CTA membrane, which increased from 27.94 nm at pH 5 to 30.70 nm at pH 9. Also, variations in the PFOA concentration from 5 to 100 mg/L did not significantly impact the membrane rejection, indicating the process's capability to handle a wide range of PFOA concentrations. When seawater was the draw solution, the FO membrane rejected 99 % of PFOA concentrations ranging from 5 mg/L to 100 mg/L. The CTA FO treating PFOA-contaminated wastewater from soil remediation achieved a 90 % recovery rate and water flux recovery of 96.5 % after cleaning with DI water at 40 °C, followed by osmotic backwash. The results suggest the potential of using abundant and cost-effective natural solutions in the FO process, all without evident membrane fouling.

Superb green cycling strategies for microbe-Fe0 neural network-type interaction: Harnessing eight key genes encoding enzymes and mineral transformations to efficiently treat PFOA

To address time-consuming and efficiency-limited challenges in conventional zero-valent iron (ZVI, Fe0) reduction or biotransformation for perfluorooctanoic acid (PFOA) treatment, two calcium alginate-embedded amendments (biochar-immobilized PFOA-degrading bacteria (CB) and ZVI (CZ)) were developed to construct microbe-Fe0 high-rate interaction systems. Interaction mechanisms and key metabolic pathways were systematically explored using metagenomics and a multi-process coupling model for PFOA under microbe-Fe0 interaction. Compared to Fe0 (0.0076 day−1) or microbe (0.0172 day−1) systems, the PFOA removal rate (0.0426 day−1) increased by 1.5 to 4.6 folds in the batch microbe-Fe0 interaction system. Moreover, Pseudomonas accelerated the transformation of Fe0 into Fe3+, which profoundly impacted PFOA transport and fate. Model results demonstrated microbe-Fe0 interaction improved retardation effect for PFOA in columns, with decreased dispersivity a (0.48 to 0.20 cm), increased reaction rate λ (0.15 to 0.22 h−1), distribution coefficient Kd (0.22 to 0.46 cm3∙g−1), and fraction f´(52 % to 60 %) of first-order kinetic sorption of PFOA in microbe-Fe0 interaction column system. Moreover, intermediates analysis showed that microbe-Fe0 interaction diversified PFOA reaction pathways. Three key metabolic pathways (ko00362, ko00626, ko00361), eight functional genes, and corresponding enzymes for PFOA degradation were identified. These findings provide insights into microbe-Fe0 “neural network-type” interaction by unveiling biotransformation and mineral transformation mechanisms for efficient PFOA treatment.

A Deep Insight into Perfluorooctanoic Acid Photodegradation Using Metal Ion-Exchanged Zeolites.

Treating perfluorooctanoic acid (PFOA) in an aqueous environment is problematic due to its low concentration and its high resistance to biological and chemical degradation. To tackle this challenge, combinations of pre-enrichment and photodegradation processes are promising solutions. In this work, we investigated metal ion-exchanged zeolites as adsorbents and photocatalysts for PFOA treatment. Among various transition metal ion-exchanged BEA zeolites, Fe-exchanged BEA (Fe-BEA) zeolites showed significant activity for the photodegradation of PFOA. The isolated iron species in Fe-BEA zeolite are responsible for PFOA photodegradation, whereas other iron species present from excess iron loading in the zeolite will lower its photocatalytic activity. Furthermore, it was proved via size exclusion tests using branched PFOA isomers that the photodegradation of PFOA took place on the internal surface rather than the external surface of Fe-BEA zeolite. Photodegradation of PFOA was also tested to be effective with Fe-exchanged BEA-type zeolites having various SiO2/Al2O3 ratios, but ineffective with FAU-type zeolites. The optimal Fe-BEA zeolite showed a sorption coefficient Kd of 6.0 × 105 L kg-1 at an aqueous phase PFOA concentration of 0.7 μg L-1 and a PFOA half-life of 1.8 h under UV-A irradiation. The presented study offers a deeper understanding of the use of metal ion-exchanged zeolites for photodegradation of PFOA.

Perfluorooctanoic acid suppresses sperm functions via abnormal Protein Kinase B activation during capacitation

Perfluorooctanoic acid (PFOA) is a perfluorinated compound, a synthesized chemical, and has been used in several industrial products for more than 70 years. Although PFOA is known to exert toxic effects in normal cells, there is no detailed information on its reproductive toxicity and its effects on sperm functions related to protein kinase B (AKT). Therefore, this study was conducted to explore the effects of PFOA on sperm functions via AKT. Boar spermatozoa were incubated with different concentrations of PFOA (0, 0.1, 1, 10, and 100 μM) to induce capacitation. Sperm functions (sperm motility, motion kinematic parameters, capacitation status, cell viability, and intracellular ATP levels) were evaluated. In addition, the expression levels of AKT, phospho-AKT, phospho-PKA, and tyrosine phosphorylated proteins were evaluated by western blotting. Results showed significant decreases in sperm motility and motion kinematic parameters. PFOA treatment significant suppressed spermatozoa capacitation and intracellular ATP levels. Furthermore, it significantly decreased the levels of phospho-PKA and tyrosine phosphorylated proteins. The levels of AKT phosphorylation at Thr308 and Ser473 also significantly decreased. These findings suggest that PFOA diminishes sperm functions during capacitation and induces unnatural phosphorylation in AKT, leading to reproductive toxicity. Therefore, people should be aware of reproductive toxicity when using PFOA.

Perfluorooctanoic acid (PFOA) inhibits steroidogenesis and mitochondrial function in bovine granulosa cells in vitro

Perfluorooctanoic acid (PFOA) is a persistent environmental contaminant. Due to the ubiquitous presence of PFOA in the environment, the impacts of PFOA exposure not only affect human reproductive health but may also affect livestock reproductive health. The focus of this study was to determine the effects of PFOA on the physiological functions of bovine granulosa cells in vitro. Primary bovine granulosa cells were exposed to 0, 4, and 40 μM PFOA for 48 and 96 h followed by analysis of granulosa cell function including cell viability, steroidogenesis, and mitochondrial activity. Results revealed that PFOA inhibited steroid hormone secretion and altered the expression of key enzymes required for steroidogenesis. Gene expression analysis revealed decreases in mRNA transcripts for CYP11A1, HSD3B, and CYP19A1 and an increase in STAR expression after PFOA exposure. Similarly, PFOA decreased levels of CYP11A1 and CYP19A1 protein. PFOA did not impact live cell number, alter the cell cycle, or induce apoptosis, although it reduced metabolic activity, indicative of mitochondrial dysfunction. We observed that PFOA treatment caused a loss of mitochondrial membrane potential and increases in PINK protein expression, suggestive of mitophagy and mitochondrial damage. Further analysis revealed that these changes were associated with increased levels of reactive oxygen species. Expression of autophagy related proteins phosphoULK1 and LAMP2 were increased after PFOA exposure, in addition to an increased abundance of lysosomes, characteristic of increased autophagy. Taken together, these findings suggest that PFOA can negatively impact granulosa cell steroidogenesis via mitochondrial dysfunction.

Ultra-high capacity, multifunctional nanoscale sorbents for PFOA and PFOS treatment

Here, we describe surface functionalized, superparamagnetic iron oxide nanocrystals (IONCs) for ultra-high PFAS sorption and precise, low energy (magnetic) separation, considering perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS). As a function of surface coating, sorption capacities described are considerably higher than previous studies using activated carbon, polymers, and unmodified metal/metal oxides, among others. In particular, positively charged polyethyleneimine (PEI) coated IONCs demonstrate extreme sorption capacities for both PFOA and PFOS due to electrostatic and hydrophobic interactions, along with high polymer grafting densities, while remaining stable in water, thus maintaining available surface area. Further, through a newly developed method using a quart crystal microbalance with dissipation (QCM-D), we present real-time, interfacial observations (e.g., sorption kinetics). Through this method, we explore underpinning mechanism(s) for differential PFAS (PFOA vs PFOS) sorption behavior(s), demonstrating that PFAS functional head group strongly influence molecular orientation on/at the sorbent interface. The effects of water chemistry, including pH, ionic composition of water, and natural organic matter on sorption behavior are also evaluated and along with material (treatment) demonstration via bench-scale column studies.

Perfluorooctanoic acid-induced cell death via the dual roles of ROS-MAPK/ERK signaling in ameloblast-lineage cells

Perfluorooctanoic acid (PFOA) is an artificial fluorinated organic compound that has generated increased public attention due to its potential health hazards. Unsafe levels of PFOA exposure can affect reproduction, growth and development. During tooth enamel development (amelogenesis), environmental factors including fluoride can cause enamel hypoplasia. However, the effects of PFOA on ameloblasts and tooth enamel formation remain largely unknown. In the present study we demonstrate several PFOA-mediated cell death pathways (necrosis/necroptosis, and apoptosis) and assess the roles of ROS-MAPK/ERK signaling in PFOA-mediated cell death in mouse ameloblast-lineage cells (ALC).ALC cells were treated with PFOA. Cell proliferation and viability were analyzed by MTT assays and colony formation assays, respectively. PFOA suppressed cell proliferation and viability in a dose dependent manner. PFOA induced both necrosis (PI-positive cells) and apoptosis (cleaved-caspase-3, γH2AX and TUNEL-positive cells). PFOA significantly increased ROS production and up-regulated phosphor-(p)-ERK. Addition of ROS inhibitor N-acetyl cysteine (NAC) suppressed p-ERK and decreased necrosis, and increased cell viability compared to PFOA alone, whereas NAC did not change apoptosis. This suggests that PFOA-mediated necrosis was induced by ROS-MAPK/ERK signaling, but apoptosis was not associated with ROS. Addition of MAPK/ERK inhibitor PD98059 suppressed necrosis and increased cell viability compared to PFOA alone. Intriguingly, PD98059 augmented PFOA-mediated apoptosis. This suggests that p-ERK promoted necrosis but suppressed apoptosis. Addition of the necroptosis inhibitor Necrostatin-1 restored cell viability compared to PFOA alone, while pan-caspase inhibitor Z-VAD did not mitigate PFOA-mediated cell death. These results suggest that 1) PFOA-mediated cell death was mainly caused by necrosis/necroptosis by ROS-MAPK/ERK signaling rather than apoptosis, 2) MAPK/ERK signaling plays the dual roles (promoting necrosis and suppressing apoptosis) under PFOA treatment. This is the initial report to indicate that PFOA could be considered as a possible causative factor for cryptogenic enamel malformation. Further studies are required to elucidate the mechanisms of PFOA-mediated adverse effects on amelogenesis.

Chronic PFOA exposure in vitro causes acquisition of multiple tumor cell characteristics in rat liver cells

Perfluorooctanoic acid (PFOA) is tumorigenic in rats and mice and potentially tumorigenic in humans. Here, we studied long-term PFOA exposure with an in vitro transformation model using the rat liver epithelial cell, TRL 1215. Cells were cultured in 10 μM (T10), 50 μM (T50) and 100 μM (T100) PFOA for 38 weeks and compared to passage-matched control cells. T100 cells showed morphological changes, loss of cell contact inhibition, formation of multinucleated giant and spindle-shaped cells. T10, T50, and T100 cells showed increased LC50 values 20%, 29% to 35% above control with acute PFOA treatment, indicating a resistance to PFOA toxicity. PFOA-treated cells showed increases in Matrix metalloproteinase-9 secretion, cell migration, and developed more and larger colonies in soft agar. Microarray data showed Myc pathway activation at T50 and T100, associating Myc upregulation with PFOA-induced morphological transformation. Western blot confirmed that PFOA produced significant increases in c-MYC protein expression in a time- and concentration-related manner. Tumor invasion indicators MMP-2 and MMP-9, cell cycle regulator cyclin D1, and oxidative stress protein GST were all significantly overexpressed in T100 cells. Taken together, chronic in vitro PFOA exposure produced multiple cell characteristics of malignant progression and differential gene expression changes suggestive of rat liver cell transformation.

Perfluorooctanoic acid (PFOA) promotes follicular growth and alters expression of genes that regulate the cell cycle and the Hippo pathway in cultured neonatal mouse ovaries

Perfluorooctanoic acid (PFOA) is a synthetic chemical resistant to biodegradation and is environmentally persistent. PFOA is found in many consumer products and is a major source of water contamination. While PFOA has been identified as a contaminant of concern for reproductive health, little is known about the effects of PFOA on ovarian follicular development and growth. Recent evidence indicates that the Hippo pathway is an important regulator of ovarian physiology. Here, we investigated the effects of PFOA on ovarian folliculogenesis during the neonatal period of development and potential impacts on the Hippo signaling pathway. Post-natal day 4 (PND4) neonatal ovaries from CD-1 mice were cultured with control medium (DMSO <0.01% final concentration) or PFOA (50 μM or 100 μM). After 96 h, ovaries were collected for histological analysis of folliculogenesis, gene and protein expression, and immunostaining. Results revealed that PFOA (50 μM) increased the number of secondary follicles, which was accompanied by increases in mRNA transcripts and protein of marker of proliferation marker Ki67 with no impacts on apoptosis markers Bax, Bcl2, or cleaved caspase-3. PFOA treatment (50 μM and 100 μM) stimulated an upregulation of transcripts for cell cycle regulators Ccna2, Ccnb2, Ccne1, Ccnd1, Ccnd2, and Ccnd3. PFOA also increased abundance of transcripts of Hippo pathway components Mst1/2, Lats1, Mob1b, Yap1, and Taz, as well as downstream Hippo pathway targets Areg, Amotl2, and Cyr61, although it decreased transcripts for anti-apoptotic Birc5. Inhibition of the Hippo pathway effector YAP1 with Verteporfin resulted in the attenuation of PFOA-induced follicular growth and proliferation. Together, these findings suggest that occupationally relevant levels of PFOA (50 μM) can stimulate follicular activation in neonatal ovaries potentially through activation of the Hippo pathway.

Perfluorooctanoic acid promotes pancreatic β cell dysfunction and apoptosis through ER stress and the ATF4/CHOP/TRIB3 pathway.

Perfluorooctanoic acid (PFOA), a widely used chemical substance, causes an increased risk of human type 2 diabetes (T2D), but its underlying mechanism is not well elucidated. The aim of the present study was to investigate whether PFOA regulates the functions of pancreatic β cells, which are specialized for the biosynthesis and secretion of insulin. The treatment of the mouse pancreatic β cell line (MIN6 cells) with PFOA caused a time- and dose-dependent inhibition of cell viability in CCK-8 assays. Annexin V/PI and TUNEL staining results confirmed that exposure to a high PFOA dose (500μM) promoted apoptosis of β cells, while a low dose (300μM) had no effects on β cell survival. PFOA treatment, even at a low dose, diminished glucose-stimulated insulin secretion (GSIS) in both primary islet perfusion and MIN6 cell experiments. RNA-sequencing data showed significantly increased expression of endoplasmic reticulum (ER) stress-associated genes, with tribbles homolog 3 (Trib3) ranking first among the altered genes. The activation of ER stress pathways was verified by qRT-PCR assays, and the ATF4/CHOP/TRIB3 pathway contributed to PFOA-induced β cell damage. The inhibition of TRIB3 expression significantly protected MIN6 cells from PFOA-induced GSIS defects and apoptosis by ameliorating ER stress. These findings reveal a link between ER stress and PFOA-induced β cell defects, opening up a new set of questions about the pathogenesis of T2D due to environmental chemicals.

Preparation of superamphiphobic stainless steel surface by laser and perfluorooctanoic acid treatment

A kind of stainless steel surface with superhydrophobic and superoleophobic were prepared by nanosecond laser. The surface of 304stainless steel was ablated by laser to obtain micro-nano structure, and then the surface energy of the sample was reduced by using the aqueous solution of perfluorooctanoic acid (PFOA) to obtain the special wettability surface. The contact angles (CA) of 5 μL of water, glycerol, peanut oil and hexadecane were 165.77°, 155.09°, 155.24° and 152.83° respectively, and the sliding angles (SA) were about 1°, 2°, 4° and 10° respectively. The surface of the sample was analyzed and characterized by SEM, EDS, FTIR and other testing equipment. The influence of single variable on wettability was studied by controlling the scanning interval, speed, heating temperature, soaking time and so on. The samples obtained by this method have good self-cleaning, wear resistance and stability, and can still maintain good superhydrophobic and superhydrophobic properties under natural conditions for up to two months.

Preparation of Superamphiphobic Stainless Steel Surface by Laser and Perfluorooctanoic Acid Treatment

Preparation of Superamphiphobic Stainless Steel Surface by Laser and Perfluorooctanoic Acid Treatment

Transcriptome analysis of 3D primary mouse liver spheroids shows that long-term exposure to hexafluoropropylene oxide trimer acid disrupts hepatic bile acid metabolism

Hexafluoropropylene oxide trimer acid (HFPO-TA), an alternative to perfluorooctanoic acid (PFOA), has been detected in various environmental and human matrices. However, information regarding its toxicity remains limited. Here, we established a three-dimensional (3D) primary mouse liver spheroid model to compare the hepatotoxicity of HFPO-TA and PFOA. The 3D spheroids were repeatedly exposed to 25-, 50-, or 100-μM HFPO-TA and PFOA for 28 d. Compared with the PFOA groups, the HFPO-TA groups showed higher bioaccumulation potential, higher lactate dehydrogenase (LDH) leakage, and lower adenosine triphosphate (ATP), albumin, and urea secretion. Transcriptome analysis identified 1603 and 772 differentially expressed genes in the 100-μM HFPO-TA- and PFOA-treated groups, respectively. Bioinformatics analysis indicated that cholesterol metabolism, bile acid metabolism, and inflammatory response were significantly altered. Exposure to 100-μM HFPO-TA increased triglyceride content but decreased total cholesterol content, while no changes were observed in the 100-μM PFOA-treated group. Total bile acids in the re-polarized 3D spheroids increased significantly after 100-μM HFPO-TA and PFOA treatment, which did not affect bile acid synthesis but inhibited the expression levels of Bsep and Mrp2 related to bile acid transport. Thus, HFPO-TA exhibited more serious hepatotoxicity than PFOA in 3D primary liver spheroids and may not be a safe alternative.

Exposure to GenX and Its Novel Analogs Disrupts Hepatic Bile Acid Metabolism in Male Mice.

Due to its wide usage and recent detection in environmental matrices, hexafluoropropylene oxide dimer acid (HFPO-DA, commercial name GenX) has attracted considerable attention. Here, we explored and compared the toxicity of GenX and its novel analogs with that of perfluorooctanoic acid (PFOA) to provide guidance on the structural design and optimization of novel alternatives to poly- and perfluoroalkyl substances (PFASs). Adult male BALB/c mice were continuously exposed to PFOA, GenX, perfluoro-2-methyl-3,6-dioxo-heptanoic acid (PFMO2HpA), and perfluoro-2-methyl-3,6,8-trioxo-nonanoic acid (PFMO3NA; 0, 0.4, 2, or 10 mg/kg/d) via oral gavage for 28 days. The PFOA, GenX, and PFMO3NA treatment groups showed an increase in relative liver weight, and bile acid metabolism was the most significantly affected pathway in all treatment groups, as shown via weighted gene coexpression network analysis. The highest total bile acid levels were observed in the 2 and 10 mg/kg/d PFMO3NA groups. The ratios of primary bile acids to all bile acids increased in the high-dose groups, while the ratios of secondary bile acids showed a downward trend. Thus, bile acid metabolism disorder may be a prominent adverse effect induced by exposure to GenX, its analogs, and PFOA. Results also showed that the hepatotoxicity of PFMO2HpA was lower than that of GenX, whereas the hepatotoxicity of PFMO3NA was stronger, suggesting that PFMO2HpA may be a potential alternative to GenX.

Perfluorooctanoic acid exposure in early pregnancy induces oxidative stress in mice uterus and liver.

This study aimed to explore the mechanism of perfluorooctanoic acid (PFOA) toxicity on the uterus and liver of mice during early pregnancy. Pregnant mice were given 0, 1, 5, 10, 20, and 40 mg/kg PFOA daily by gavage from gestational day (GD) 1-7 and sacrificed on GD 9. Subsequently, several toxicity parameters were evaluated, including the uterus and liver weights, liver and uterine indexes, histopathological changes of the liver and uterus, and levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in the liver. We also determined the expressions of FAS, FASL, Bax, Bcl-2, and Caspase-3 in decidual cells by immunohistochemistry and the TUNEL assay to detect apoptosis uterine cells. The results showed that PFOA increased the liver weights and reduced the uterus index in a dose-dependent manner. With increasing doses of PFOA, the levels of SOD and GSH-Px were significantly decreased, and MDA increased substantially in liver tissue. 20 mg/kg and 40 mg/kg of PFOA caused more substantial harm to the uterus, thus a higher probability for congestion and resorption. The expression of FAS, FASL, Bax, and Caspase-3 in decidual cells of the uterus in the PFOA treatment groups significantly increased in a dose-dependent manner. The expression of Bcl-2 was downregulated, decreasing the Bcl-2/Bax ratio. At gestation day 9, the control group had significantly fewer apoptotic cells in the uterus and shallower staining than the 40 mg/kg PFOA group. The findings of this study suggest that oxidative damage may be one of the mechanisms by which PFOA induces liver toxicity, and a subsequent increase in uterine cell apoptosis may cause embryo loss or damage.

Effects of Perfluorooctanoic Acid (PFOA) and Perfluorooctane Sulfonic Acid (PFOS) on Soil Microbial Community.

The extensive application of perfluoroalkyl and polyfluoroalkyl substances (PFASs) causes their frequent detection in various environments. In this work, two typical PFASs, perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), are selected to investigate their effects on soil microorganisms. Microbial community structure and microbe-microbe relationships were investigated by high-throughput sequencing and co-occurrence network analysis. Under 90days of exposure, the alpha-diversity of soil microbial communities was increased with the PFOS treatment, followed by the PFOA treatment. The exposure of PFASs substantially changed the compositions of soil microbial communities, leading to the enrichment of more PFASs-tolerant bacteria, such as Proteobacteria, Burkholderiales, and Rhodocyclales. Comparative co-occurrence networks were constructed to investigate the microbe-microbe interactions under different PFASs treatments. The majority of nodes in the PFOA and PFOS networks were associated with the genus Azospirillum and Hydrogenophaga, respectively. The LEfSe analysis further identified a set of biomarkers in the soil microbial communities, such as Azospirillum, Methyloversatilis, Hydrogenophaga, Pseudoxanthomonas, and Fusibacter. The relative abundances of these biomarkers were also changed by different PFASs treatments. Functional gene prediction suggested that the microbial metabolism processes, such as nucleotide transport and metabolism, cell motility, carbohydrate transport and metabolism, energy production and conversion, and secondary metabolites biosynthesis transport and catabolism, might be inhibited under PFAS exposure, which may further affect soil ecological services.

Perfluorooctanoic acid induces liver and serum dyslipidemia in humanized PPARα mice fed an American diet

Per- and polyfluoroalkyl substances (PFAS) are pervasive in the environment resulting in nearly universal detection in people. Human serum PFAS concentrations are strongly associated with increased serum low-density lipoprotein cholesterol (LDL-C), and growing evidence suggests an association with serum triacylglycerides (TG). Here, we tested the hypothesis that perfluorooctanoic acid (PFOA) dysregulates liver and serum triacylglycerides in human peroxisome proliferator activated receptor α (hPPARα)-expressing mice fed an American diet. Mice were exposed to PFOA (3.5 mg/L) in drinking water for 6 weeks resulting in a serum concentration of 48 ± 9 μg/ml. In male and female hPPARα mice, PFOA increased total liver TG and TG substituted with saturated and monounsaturated fatty acids. Lack of expression of PPARα alone also increased total liver TG, and PFOA treatment had little effect on liver TG in PPARα null mice. In hPPARα mice, PFOA neither significantly increased nor decreased serum TG; however, there was a modest increase in TG associated with very low-density cholesterol particles in both sexes. Intriguingly, in female PPARα null mice, PFOA significantly increased serum TG, with a similar trend in males. PFOA also modified fatty acid and TG homeostasis-related gene expression in liver, in a hPPARα-dependent manner, but not in adipose. The results of our study and others reveal the importance of context (serum concentration and genotype) in determining the effect of PFOA on lipid homeostasis.

Metabolic profiling in human SH-SY5Y neuronal cells exposed to perfluorooctanoic acid (PFOA)

Perfluorooctanoic acid (PFOA) is an abundant per- and polyfluoroalkyl substance (PFAS) detected in both indoor and outdoor environments. While studies suggest exposure concerns for humans, studies investigating PFOA-induced neurotoxicity are lacking. To address this gap, we exposed differentiated human SH-SY5Y cells to PFOA (0.1 μM up to 500 μM) at different time points (4, 24, 48, and 72 h) and measured cell viability, Casp3/7 activity, ATP levels, ATP synthase enzyme activity, mitochondrial membrane potential, reactive oxygen species (ROS), oxygen consumption rates for mitochondrial stress test (XFe24 Flux analyzer), glucose utilization, and global metabolome profiles to assess the potential for PFOA-induced neurotoxicity. Treatment with 10 or 100 μM PFOA did not compromise cell viability nor induce cytotoxicity to SH-SY5Y cells over a 48-hour exposure period. However, >250 μM PFOA compromised cell viability, induced cytotoxicity, and induced caspase 3/7 activity at 48 h. ATP levels were reduced in cells treated with 400 μM PFOA for 24 and 48 h, and with 100 μM PFOA and higher at 72 h. ATP synthase activity was inhibited by 250 μM PFOA but was unchanged by PFOA treatment at 200 μM or less. Conversely, mitochondrial membrane potential was reduced by >10 μM PFOA after 24 h. Total ROS was increased with 100 μM PFOA and higher after 4 h of exposure. Several mitochondria-related endpoints (basal respiration, ATP production, maximum respiration) were negatively affected at 250 μM PFOA at both 24- and 48-hour exposure, but were unaltered at concentrations of 100 μM PFOA or less. One exception was mitochondrial spare capacity, which was reduced by 100 μM PFOA after 24-hour exposure. Similarly, glycolysis, glycolytic capacity, and glycolytic reserve of SH-SY5Y cells were not altered by 10 nor 100 μM PFOA. Nontargeted metabolomics was conducted in cells treated with either 10 or 100 μM PFOA for 48 h, as these two concentrations were not cytotoxic and 28 metabolites differed among treatments. Notable was that 10 μM PFOA had little effect on the SH-SY5Y metabolome, and the metabolic profile was not statistically different from media nor solvent controls. On the other hand, 100 μM PFOA shifted the metabolic signature of the neuronal cells, leading to reduced abundance of ATP-related metabolites (adenine, nicotinamide), neurotransmitter precursors (DL-tryptophan, l-tyrosine), and metabolites that protect mitochondria during oxidative stress (betaine, orotic acid, and l-acetyl carnitine). We hypothesize that this metabolic signature may be associated with the reduced mitochondrial membrane potential observed at lower PFOA concentrations. Metabolic shifts appear to precede compromised cell viability, cytotoxicity, and apoptosis. This study generates mechanistic knowledge regarding PFOA-induced neurotoxicity, focusing on mitochondrial oxidative respiration and the neuronal metabolome.