Frontiers in toxicologyPub Date : 2024-08-06eCollection Date: 2024-01-01DOI: 10.3389/ftox.2024.1397477
S Spulber, L Reis, P Alexe, S Ceccatelli
{"title":"Decreased activity in zebrafish larvae exposed to glyphosate-based herbicides during development-potential mediation by glucocorticoid receptor.","authors":"S Spulber, L Reis, P Alexe, S Ceccatelli","doi":"10.3389/ftox.2024.1397477","DOIUrl":"10.3389/ftox.2024.1397477","url":null,"abstract":"<p><p>Glyphosate-based herbicides (GBH) are a widely used group of pesticides that have glyphosate (GLY) as main active compound and are used to control a wide range of weeds. Experimental and epidemiological studies point to neurotoxicity and endocrine disruption as main toxic effects. The aim of this study was to investigate the effects of developmental exposure to GLY and GBH on locomotor behavior, and the possible contribution of GR-mediated signaling. We used zebrafish (<i>Danio rerio</i>) larvae in a continuous exposure regimen to GLY or GBH in the rearing medium. Alongside TL wildtype, we used a mutant line carrying a mutation in the GR which prevents the GR from binding to DNA (gr<sup>s357</sup>), as well as a transgenic strain expressing a variant of enhanced green fluorescent protein (d4eGFP) controlled by a promoter carrying multiple GR response elements (SR4G). We found that acute exposure to GBH, but not GLY, activates GR-mediated signaling. Using a continuous developmental exposure regime, we show that wildtype larvae exposed to GBH display decreased spontaneous activity and attenuated response to environmental stimuli, a pattern of alteration similar to the one observed in gr<sup>s357</sup> mutant larvae. In addition, developmental exposure to GBH has virtually no effects on the behavior of gr<sup>s357</sup> mutant larvae. Taken together, our data indicate that developmental exposure to GBH has more pronounced effects than GLY on behavior at 5 dpf, and that interference with GR-mediated signaling may have a relevant contribution.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142010034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in toxicologyPub Date : 2024-08-05eCollection Date: 2024-01-01DOI: 10.3389/ftox.2024.1416708
Triana Acevedo-Huergo, Jonathan Sánchez-Yépez, María Soledad Mendoza-Trejo, Isela Hernández-Plata, Magda Giordano, Verónica Mireya Rodríguez
{"title":"Hypoactivity and neurochemical alterations in the basal ganglia of female Sprague-Dawley rats after repeated exposure to atrazine.","authors":"Triana Acevedo-Huergo, Jonathan Sánchez-Yépez, María Soledad Mendoza-Trejo, Isela Hernández-Plata, Magda Giordano, Verónica Mireya Rodríguez","doi":"10.3389/ftox.2024.1416708","DOIUrl":"10.3389/ftox.2024.1416708","url":null,"abstract":"<p><p>The herbicide atrazine (ATR) has been one of the most widely used herbicides worldwide. However, due to its indiscriminate use, it has been considered an environmental contaminant. Several studies have classified ATR as an endocrine disruptor, and it has been found to have neurotoxic effects on behavior, along with alterations in the dopaminergic, GABAergic, and glutamatergic systems in the basal ganglia of male rodents. These findings suggest that these neurotransmitter systems are targets of this herbicide. However, there are no studies evaluating the neurotoxicity of ATR in female rodents. Our study aimed to assess the effects of repeated IP injections of 100 mg ATR/kg or a vehicle every other day for 2 weeks (six injections) on the locomotor activity, content of monoamines, GABA, glutamate, and glutamine in the striatum, nucleus accumbens, ventral midbrain, and prefrontal cortex, and tyrosine hydroxylase (TH) protein levels in striatum and nucleus accumbens of female rats. Repeated 100 mg ATR/kg injections immediately decreased all the locomotor activity parameters evaluated, and such hypoactivity persisted for at least 48 h after the last ATR administration. The ATR administration increased dopamine and DOPAC content in the nucleus accumbens and the dopamine and DOPAC and serotonin and 5-HIAA content in the ventral midbrain. In contrast, the TH protein levels in the striatum and nucleus accumbens were similar between groups. Meanwhile, GABA, glutamine, and glutamate levels remained unaltered in all brain regions evaluated. The observed behavioral alterations could be associated with the monoamine changes presented by the rats. These data reveal that the nucleus accumbens and ventral midbrain are susceptible to repeated ATR exposure in female rats.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11330890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142006083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in toxicologyPub Date : 2024-07-29eCollection Date: 2024-01-01DOI: 10.3389/ftox.2024.1331803
Rita Hargitai, Lucia Parráková, Tünde Szatmári, Pablo Monfort-Lanzas, Valentina Galbiati, Karine Audouze, Florence Jornod, Yvonne C M Staal, Sabina Burla, Aline Chary, Arno C Gutleb, Katalin Lumniczky, Rob J Vandebriel, Johanna M Gostner
{"title":"Chemical respiratory sensitization-Current status of mechanistic understanding, knowledge gaps and possible identification methods of sensitizers.","authors":"Rita Hargitai, Lucia Parráková, Tünde Szatmári, Pablo Monfort-Lanzas, Valentina Galbiati, Karine Audouze, Florence Jornod, Yvonne C M Staal, Sabina Burla, Aline Chary, Arno C Gutleb, Katalin Lumniczky, Rob J Vandebriel, Johanna M Gostner","doi":"10.3389/ftox.2024.1331803","DOIUrl":"10.3389/ftox.2024.1331803","url":null,"abstract":"<p><p>Respiratory sensitization is a complex immunological process eventually leading to hypersensitivity following re-exposure to the chemical. A frequent consequence is occupational asthma, which may occur after long latency periods. Although chemical-induced respiratory hypersensitivity has been known for decades, there are currently no comprehensive and validated approaches available for the prospective identification of chemicals that induce respiratory sensitization, while the expectations of new approach methodologies (NAMs) are high. A great hope is that due to a better understanding of the molecular key events, new methods can be developed now. However, this is a big challenge due to the different chemical classes to which respiratory sensitizers belong, as well as because of the complexity of the response and the late manifestation of symptoms. In this review article, the current information on respiratory sensitization related processes is summarized by introducing it in the available adverse outcome pathway (AOP) concept. Potentially useful models for prediction are discussed. Knowledge gaps and gaps of regulatory concern are identified.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11317441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Near-cure in patients with Gadolinium deposition disease undergoing intravenous DTPA chelation","authors":"R. Semelka, M. Ramalho","doi":"10.3389/ftox.2024.1371131","DOIUrl":"https://doi.org/10.3389/ftox.2024.1371131","url":null,"abstract":"To demonstrate and evaluate factors contributing to near-cures in patients with Gadolinium Deposition Disease (GDD) undergoing intravenous (IV) DTPA chelation.Patients who had undergone or are currently undergoing DTPA chelation for GDD were included in this report based on their medical records that showed their perceived improvement was at least 80% back to normal. A survey was developed that included factors commonly reported by patients treated in one clinic to determine if these ‘near-cured’ (pre-MRI baseline health) individuals possessed certain factors and lacked others. The anonymized survey was emailed to these individuals by the principal treating physician, the only investigator not blinded to the subjects. This report describes clinical documentation of patient status and their underlying factors in individuals treated by the primary author, and no research was performed. The survey was sent to sixteen individuals; Fourteen patients completed it (10 females; 41.1 ± 11.2 y/o).The most common factor was the administration of ≤5 lifetime doses of a Gadolinium-Based Contrast Agents (GBCA) (12/14). Unconfounded agents triggering GDD were seen in nine subjects. Most subjects (12/14) initiated chelation in the first year after the causative GBCA, and most (11/14) underwent ≤10 chelations with DTPA. Good healthcare status prior to MRI was observed in 5 subjects. The majority (11/14) described their immune status as strong. Severe physical disability prior to chelation was seen in 1.Subjects with GDD can experience near-cure with IV DTPA chelation. Factors surveyed that predict near-cure include the start of chelation in the first year, few GBCA administrations, and good health status before MRI with GBCA injection. Nonetheless, a few patients with predictors of less successful outcomes still experienced near-cure.","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141806320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I. Cattani-Cavalieri, Marina Trombetta-Lima, Hong Yan, Ana L. Manzano-Covarrubias, H. Baarsma, Asmaa Oun, Melissa Mol van der Veen, Emily Oosterhout, Amalia M. Dolga, R. Ostrom, S. Valença, Martina Schmidt
{"title":"Diesel exhaust particles alter mitochondrial bioenergetics and cAMP producing capacity in human bronchial epithelial cells","authors":"I. Cattani-Cavalieri, Marina Trombetta-Lima, Hong Yan, Ana L. Manzano-Covarrubias, H. Baarsma, Asmaa Oun, Melissa Mol van der Veen, Emily Oosterhout, Amalia M. Dolga, R. Ostrom, S. Valença, Martina Schmidt","doi":"10.3389/ftox.2024.1412864","DOIUrl":"https://doi.org/10.3389/ftox.2024.1412864","url":null,"abstract":"Introduction: Air pollution from diesel combustion is linked in part to the generation of diesel exhaust particles (DEP). DEP exposure induces various processes, including inflammation and oxidative stress, which ultimately contribute to a decline in lung function. Cyclic AMP (cAMP) signaling is critical for lung homeostasis. The impact of DEP on cAMP signaling is largely unknown.Methods: We exposed human bronchial epithelial (BEAS-2B) cells to DEP for 24–72 h and evaluated mitochondrial bioenergetics, markers of oxidative stress and inflammation and the components of cAMP signaling. Mitochondrial bioenergetics was measured at 72 h to capture the potential and accumulative effects of prolonged DEP exposure on mitochondrial function.Results: DEP profoundly altered mitochondrial morphology and network integrity, reduced both basal and ATP-linked respiration as well as the glycolytic capacity of mitochondria. DEP exposure increased gene expression of oxidative stress and inflammation markers such as interleukin-8 and interleukin-6. DEP significantly affected mRNA levels of exchange protein directly activated by cAMP-1 and -2 (Epac1, Epac2), appeared to increase Epac1 protein, but left phospho-PKA levels unhanged. DEP exposure increased A-kinase anchoring protein 1, β2‐adrenoceptor and prostanoid E receptor subtype 4 mRNA levels. Interestingly, DEP decreased mRNA levels of adenylyl cyclase 9 and reduced cAMP levels stimulated by forskolin (AC activator), fenoterol (β2-AR agonist) or PGE2 (EPR agonist).Discussion: Our findings suggest that DEP induces mitochondrial dysfunction, a process accompanied by oxidative stress and inflammation, and broadly dampens cAMP signaling. These epithelial responses may contribute to lung dysfunction induced by air pollution exposure.","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141803334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Rogers, E. K. Breathwaite, T. Nguyen-Jones, S. M. Anderson, J. Odanga, D. T. Parks, K. Wolf, T. Stone, P. Balbuena, J. Chen, S. Presnell, J. R. Weaver, E. LeCluyse
{"title":"Characterization of a human thyroid microtissue model for testing thyroid disrupting chemicals","authors":"E. Rogers, E. K. Breathwaite, T. Nguyen-Jones, S. M. Anderson, J. Odanga, D. T. Parks, K. Wolf, T. Stone, P. Balbuena, J. Chen, S. Presnell, J. R. Weaver, E. LeCluyse","doi":"10.3389/ftox.2024.1408808","DOIUrl":"https://doi.org/10.3389/ftox.2024.1408808","url":null,"abstract":"Perturbation of thyroid hormone (T4) synthesis is known to cause numerous developmental, metabolic, and cognitive disorders in humans. Due to species differences in sensitivity to chemical exposures, there is a need for human-based in vitro approaches that recapitulate thyroid cellular architecture and T4 production when screening. To address these limitations, primary human thyrocytes, isolated from healthy adult donor tissues and cryopreserved at passage one (p’1) were characterized for cellular composition, 3D follicular architecture, and thyroglobulin (TG)/T4 expression and inhibition by prototype thyroid disrupting chemicals (TDC). Flow analysis of the post-thaw cell suspension showed >80% EpCAM-positive cells with 10%–50% CD90-positive cells. When seeded onto 96-well Matrigel®-coated plates and treated with bovine thyroid stimulating hormone (TSH), thyrocytes formed 3D microtissues during the initial 4–5 days of culture. The microtissues exhibited a stable morphology and size over a 14-day culture period. TG and T4 production were highest in microtissues when the proportion of CD90-positive cells, seeding density and thyroid stimulating hormone concentrations were between 10%–30%, 6K–12K cells per well, and 0.03–1 mIU/mL, respectively. At maximal TG and T4 production levels, average microtissue diameters ranged between 50 and 200 µm. The T4 IC50 values for two prototype TPO inhibitors, 6-propyl-2-thiouracil and methimazole, were ∼0.7 µM and ∼0.5 µM, respectively, in microtissue cultures treated between days 9 and 14. Overall, p’1 cryopreserved primary human thyrocytes in 3D microtissue culture represent a promising new model system to prioritize potential TDC acting directly on the thyroid as part of a weight-of-evidence hazard characterization.","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141809828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gelsomina Pillo, Federico Aldrovandi, Ada Mescoli, Giangabriele Maffei, M. Mascolo, Monica Vaccari, A. Colacci
{"title":"An insight into carcinogenic activity and molecular mechanisms of Bis(2-ethylhexyl) phthalate","authors":"Gelsomina Pillo, Federico Aldrovandi, Ada Mescoli, Giangabriele Maffei, M. Mascolo, Monica Vaccari, A. Colacci","doi":"10.3389/ftox.2024.1389160","DOIUrl":"https://doi.org/10.3389/ftox.2024.1389160","url":null,"abstract":"Di(ethylhexyl) phthalate (DEHP) is a ubiquitous environmental contaminant to which humans are exposed via multiple routes. Human health risk assessments for this substance have recently been updated, focusing on reproductive toxicity, including DEHP, in the list of chemicals classified as carcinogenic, mutagenic, or toxic to reproduction (CMR). Moreover, DEHP has also been defined as probably and possibly carcinogenic to humans based on its carcinogenicity in rodents. However, the mechanism of action of DEHP and its relevance in humans remain unclear. Rodent data suggests that DEHP induces cancer through non-genotoxic mechanisms related to multiple molecular signals, including PPARα activation, perturbation of fatty acid metabolism, induction of cell proliferation, decreased apoptosis, production of reactive oxygen species, and oxidative stress. According to the DEHP toxicological dataset, several in vitro cell transformation assays have been performed using different protocols and cellular models to produce different results. This study aimed to evaluate the carcinogenic potential of DEHP by using the A31-1-1 BALB/c-3T3 cell line in a standard cell transformation assay. Additionally, transcriptomic analysis was performed to explore the molecular responses and identify the affected toxicological pathways. Although DEHP treatment did not induce transformation in BALB/c-3T3 cells, the transcriptomic results revealed significant modulation of several pathways associated with DEHP metabolism, tissue-specific functions related to systemic metabolism, and basal cellular signaling with pleiotropic outcomes. Among these signaling pathways, modulation of cell-regulating signaling pathways, such as Notch, Wnt, and TGF-β, can be highlighted. More specific modulation of such genes and pathways with double functions in metabolism and neurophysiology underlies the well-known crosstalk that may be crucial for the mechanism of action of DEHP. Our findings offer evidence to support the notion that these models are effective in minimizing the use of animal testing for toxicity assessment.","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141813826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mahmoud G. Soliman, Alberto Martinez-Serra, Marko Dobricic, Duong N. Trinh, Jack Cheeseman, Daniel I R Spencer, M. Monopoli
{"title":"Protocols for isolation and characterization of nanoparticle biomolecular corona complexes","authors":"Mahmoud G. Soliman, Alberto Martinez-Serra, Marko Dobricic, Duong N. Trinh, Jack Cheeseman, Daniel I R Spencer, M. Monopoli","doi":"10.3389/ftox.2024.1393330","DOIUrl":"https://doi.org/10.3389/ftox.2024.1393330","url":null,"abstract":"Engineered nanoparticles (NPs) pose a broad spectrum of interesting properties that make them useful for many applications. However, continuous exposure to NPs requires the need to deeply understand the outcomes when these NPs interact with different biological environments. After exposure within (to) these environments, the pristine surfaces of NPs strongly interact with the molecules from the surrounding medium, including metabolites, lipids, glycan, and proteins, forming the so-called protein corona (PC). It is well established that the NP-PC strongly influences the biological fate of various NPs types, including cellular uptake, toxicity, and biodistribution. Thus, for a proper assessment of potential hazards associated with engineered NPs, it is mandatory to study and evaluate the PC that forms around NPs. Herein, we describe protocols in detail for the isolation and characterization of NP-PC complexes and cover the following aspects: 1) isolation protocols for different nanomaterials in a range of exposing media, including magnetic isolation methods for superparamagnetic NPs, 2) NP physico-chemical characterization using advanced and standard techniques available in regular laboratories, and 3) NP- PC characterization of the protein and glycan components.","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141812507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brent Wyatt, A. P. Davis, Thomas C. Wiegers, Jolene Wiegers, Sakib Abrar, D. Sciaky, Fern Barkalow, Melissa Strong, C. Mattingly
{"title":"Transforming environmental health datasets from the comparative toxicogenomics database into chord diagrams to visualize molecular mechanisms","authors":"Brent Wyatt, A. P. Davis, Thomas C. Wiegers, Jolene Wiegers, Sakib Abrar, D. Sciaky, Fern Barkalow, Melissa Strong, C. Mattingly","doi":"10.3389/ftox.2024.1437884","DOIUrl":"https://doi.org/10.3389/ftox.2024.1437884","url":null,"abstract":"In environmental health, the specific molecular mechanisms connecting a chemical exposure to an adverse endpoint are often unknown, reflecting knowledge gaps. At the public Comparative Toxicogenomics Database (CTD; https://ctdbase.org/), we integrate manually curated, literature-based interactions from CTD to compute four-unit blocks of information organized as a potential step-wise molecular mechanism, known as “CGPD-tetramers,” wherein a chemical interacts with a gene product to trigger a phenotype which can be linked to a disease. These computationally derived datasets can be used to fill the gaps and offer testable mechanistic information. Users can generate CGPD-tetramers for any combination of chemical, gene, phenotype, and/or disease of interest at CTD; however, such queries typically result in the generation of thousands of CGPD-tetramers. Here, we describe a novel approach to transform these large datasets into user-friendly chord diagrams using R. This visualization process is straightforward, simple to implement, and accessible to inexperienced users that have never used R before. Combining CGPD-tetramers into a single chord diagram helps identify potential key chemicals, genes, phenotypes, and diseases. This visualization allows users to more readily analyze computational datasets that can fill the exposure knowledge gaps in the environmental health continuum.","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141815234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yvonne Rericha, Lindsey St. Mary, Lisa Truong, Ryan McClure, J. K. Martin, Scott W. Leonard, Preethi Thunga, Michael T. Simonich, Katrina M. Waters, Jennifer A. Field, R. Tanguay
{"title":"Diverse PFAS produce unique transcriptomic changes linked to developmental toxicity in zebrafish","authors":"Yvonne Rericha, Lindsey St. Mary, Lisa Truong, Ryan McClure, J. K. Martin, Scott W. Leonard, Preethi Thunga, Michael T. Simonich, Katrina M. Waters, Jennifer A. Field, R. Tanguay","doi":"10.3389/ftox.2024.1425537","DOIUrl":"https://doi.org/10.3389/ftox.2024.1425537","url":null,"abstract":"Per- and polyfluoroalkyl substances (PFAS) are a widespread and persistent class of contaminants posing significant environmental and human health concerns. Comprehensive understanding of the modes of action underlying toxicity among structurally diverse PFAS is mostly lacking. To address this need, we recently reported on our application of developing zebrafish to evaluate a large library of PFAS for developmental toxicity. In the present study, we prioritized 15 bioactive PFAS that induced significant morphological effects and performed RNA-sequencing to characterize early transcriptional responses at a single timepoint (48 h post fertilization) after early developmental exposures (8 h post fertilization). Internal concentrations of 5 of the 15 PFAS were measured from pooled whole fish samples across multiple timepoints between 24–120 h post fertilization, and additional temporal transcriptomics at several timepoints (48–96 h post fertilization) were conducted for Nafion byproduct 2. A broad range of differentially expressed gene counts were identified across the PFAS exposures. Most PFAS that elicited robust transcriptomic changes affected biological processes of the brain and nervous system development. While PFAS disrupted unique processes, we also found that similarities in some functional head groups of PFAS were associated with the disruption in expression of similar gene sets. Body burdens after early developmental exposures to select sulfonic acid PFAS, including Nafion byproduct 2, increased from the 24–96 h post fertilization sampling timepoints and were greater than those of sulfonamide PFAS of similar chain lengths. In parallel, the Nafion byproduct 2-induced transcriptional responses increased between 48 and 96 h post fertilization. PFAS characteristics based on toxicity, transcriptomic effects, and modes of action will contribute to further prioritization of PFAS structures for testing and informed hazard assessment.","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141814026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}