Ecotoxicology and Environmental Safety最新文献

{"title":"Impact of placental microplastics on birth anthropometrics: A cross-sectional study","authors":"Ying Shen ,&nbsp;Yifan Ning ,&nbsp;Fangyuan Chen ,&nbsp;Xiaoyan Wang ,&nbsp;Dongming Zheng ,&nbsp;Yanli Sun ,&nbsp;Xiaowen Zhang ,&nbsp;Xue Zhang","doi":"10.1016/j.ecoenv.2025.119572","DOIUrl":"10.1016/j.ecoenv.2025.119572","url":null,"abstract":"<div><div>Despite growing concern about microplastic contamination in human tissues, the relationship between placental microplastic exposure and fetal anthropometric outcomes remains unexplored. This study investigated associations between placental microplastic content and birth weight (BW), birth length (BL), and head circumference (HC), in a large prospective cohort in China. We recruited 1750 mother–infant pairs between 2022–2024. Placental tissues were collected immediately after delivery from maternal and fetal sides using strict contamination-prevention protocols. Microplastics were identified and quantified via laser direct infrared (LD-IR) chemical imaging. Associations between polymer-specific microplastics (PVC, PP, PBS, PET) and fetal growth were assessed using multivariable linear regression, sex-stratified analyses, and mixture models, including g-computation (g-comp), generalized weighted quantile sum regression (gWQS), and Bayesian kernel machine regression (BKMR). Median placental microplastic concentrations were 7.0, 5.0, 4.0, and 3.0 particles/10 g tissue for PVC, PP, PBS, and PET, respectively. Higher microplastic exposure was consistently associated with reduced BW, BL, and HC. Total MPs were linked to a 107.7 g decrease in BW (95 % CI: –138.87, –76.49; p &lt; 0.001). Sex-stratified analyses showed stronger effects in male infants, particularly for BW (p-interaction = 0.04). Mixture analyses indicated cumulative negative effects across polymers. The g-comp approach estimated a BW reduction of –117.7 g (95 % CI: –155.3, –80.1) and a BL decrease of –0.89 cm (95 % CI: –1.20, –0.58). The gWQS model produced comparable estimates for BW (–100.9 g, 95 % CI: –146.2, –55.5) and BL (–0.96 cm, 95 % CI: –1.34, –0.58), while BKMR confirmed monotonic negative associations for BW, BL, and HC, with PBS and PP contributing most to the mixture effect. Placental microplastic exposure is associated with impaired fetal growth, with boys appearing more vulnerable. Future studies should investigate biological mechanisms and long-term outcomes.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"309 ","pages":"Article 119572"},"PeriodicalIF":6.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145916422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic thyroid disruption and reproductive toxicity induced by co-exposure of triadimefon and copper in zebrafish embryos","authors":"Chao Xu ,&nbsp;Yuanjing Sun ,&nbsp;Wenjie Bian ,&nbsp;Shenqi Huang ,&nbsp;Yue Peng ,&nbsp;Zili Guo ,&nbsp;Ruijiong Wang ,&nbsp;Weiping Liu ,&nbsp;Lili Niu","doi":"10.1016/j.ecoenv.2026.119713","DOIUrl":"10.1016/j.ecoenv.2026.119713","url":null,"abstract":"<div><div>The co-occurrence of pesticides and heavy metals in aquatic ecosystem poses a significant threat to biota, yet the interactive toxicological effects and mechanisms remain poorly understood, especially during their early developmental stages. In this study, we employed zebrafish embryos as a sensitive model to investigate the combined effects of fungicide triadimefon (TDF) and copper (Cu^2 +) on endocrine regulation via the hypothalamus-pituitary-thyroid (HPT) and hypothalamus-pituitary-gonadal (HPG) axes. Our results showed that both individual and combined exposures to TDF and Cu²⁺ significantly increased the mortality and malformation rates, impaired swimming ability, and exhibited dose-dependent toxicity. Compared to Cu²⁺ exposure alone, TDF exposure significantly reduced thyroxine (T4) levels in zebrafish, and the co-exposure further exacerbated this reduction. Cu²⁺ alone downregulated several HPT-related genes (e.g., <em>TTR</em>), whereas TDF exposure and co-exposure upregulated <em>TTR</em> expression. Regarding reproductive toxicity, Cu²⁺ exhibited a stronger inhibitory effect on key HPG genes (e.g., <em>cyp19a</em>) compared to TDF; however, co-exposure significantly enhanced these inhibitory and induced the upregulation of genes such as <em>StAR</em>. The results of this study provide insights into the dual disruption of thyroid and reproductive endocrine functions by TDF and Cu²⁺, improveing our understanding of the combined ecological risks posed by pesticide and heavy metal co-contamination.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"309 ","pages":"Article 119713"},"PeriodicalIF":6.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shaping a pro-carcinogenic hepatic microenvironment by TCDD: An integrated approach combining network toxicology, machine learning, molecular docking, molecular dynamics and experimental validation","authors":"Yuanyuan Sun ,&nbsp;Jingjing Ma ,&nbsp;Xinrui Zhou ,&nbsp;Renting Cao ,&nbsp;Meng Su ,&nbsp;Shenao Li ,&nbsp;Xiaolong Lu ,&nbsp;Daiyin Peng ,&nbsp;Jing Zhang ,&nbsp;Can Peng ,&nbsp;Jia Lu","doi":"10.1016/j.ecoenv.2026.119708","DOIUrl":"10.1016/j.ecoenv.2026.119708","url":null,"abstract":"<div><div>The increasing prevalence of environmental contaminants has raised concerns regarding their potential contribution to hepatic dysfunction and associated diseases. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), classified as a Group 1 carcinogen and the most toxic congener of dioxins, has been implicated in adverse hepatic outcomes. However, the molecular mechanisms by which TCDD-driven signaling cascades establish a pro-carcinogenic microenvironment in the liver remain insufficiently elucidated. By integrating network toxicology with machine learning, CYP1A2, CYP2C9, and HSP90AB1 were identified as the core targets of TCDD-elicited hepatocellular carcinoma (HCC). Stable complex formation between TCDD and each target, exhibiting low conformational flexibility and robust binding affinity, was revealed through molecular docking and molecular dynamics simulations. Subsequently, TCDD-elicited hepatotoxic effects were predominantly demonstrated by Protein-Protein Interaction (PPI), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and immune infiltration analyses to be mediated via activation of chemical carcinogenesis-receptor signaling pathways, perturbation of lipid metabolism, and disruption of immune microenvironment homeostasis. In male C57BL/6 J mice, TCDD exposure was associated with significantly elevated serum markers indicative of hepatocellular injury, metabolic dysfunction, systemic inflammation, and pre-neoplastic transformation, together with markedly disturbed oxidative-stress indices. Then, histopathological examination revealed disrupted hepatic cords, collagen deposition, lipid accumulation, and widespread apoptosis, further complemented by glycogen metabolic disturbances, enhanced proliferation, and elevated pre-neoplastic biomarkers, which collectively established a pro-carcinogenic hepatic microenvironment. Immunofluorescence results indicated significant promotion of M1 (pro-inflammatory) macrophage polarization and suppression of M2 (anti-inflammatory) phenotypes, resulting in an increased M1/M2 ratio and a pro-inflammatory microenvironment. Consistently, down-regulation of CYP1A2 and CYP2C9 and up-regulation of HSP90AB1 were shown by immunofluorescence/Western blotting/RT-qPCR, impairing signaling networks and immune homeostasis and ultimately leading to the establishment of hepatotoxicity and carcinogenic microenvironments. Collectively, the TCDD “target binding-pathway dysregulation-immune imbalance-pathological damage” cascade has been systematically delineated, providing novel targets and a theoretical framework for therapeutic intervention against pollutant-associated liver diseases.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"309 ","pages":"Article 119708"},"PeriodicalIF":6.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PFOA and PFOS impair human sperm capacitation by inducing mitochondrial-mediated apoptosis and ferroptosis","authors":"Linmei Gao ,&nbsp;Nanxu Pan ,&nbsp;Wenting Xu ,&nbsp;Guoqiang Li ,&nbsp;Kun Li ,&nbsp;Jing Shi ,&nbsp;Peibei Sun","doi":"10.1016/j.ecoenv.2026.119743","DOIUrl":"10.1016/j.ecoenv.2026.119743","url":null,"abstract":"<div><div>Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), two predominant per- and polyfluoroalkyl substances, are ubiquitous environmental contaminants that have been implicated in male infertility. However, the effects and underlying mechanisms of these compounds during human sperm capacitation remain unclear. In this study, human spermatozoa were exposed to PFOA and PFOS during capacitation. Acrosome reaction and sperm viability were assessed by flow cytometry. Sperm motility and hyperactivation were assessed using computer-assisted sperm analysis. Proteomic and phosphoproteomic profiling was performed after exposure to PFOS or PFOA. Based on omics results, mitochondrial function, including mitochondrial membrane potential (Δψm) and mitochondrial permeability transition pore (MPTP) opening, was further evaluated. Antioxidant enzyme activities and non-enzymatic antioxidant levels were quantified, alongside biomarkers of apoptosis and ferroptosis. Our results demonstrated that PFOA and PFOS impaired hyperactivation and acrosome reaction while increasing sperm mortality. Proteomic and phosphoproteomic analyses revealed that PFOA and PFOS disrupted sperm capacitation through mitochondrial dysfunction and ATP dysregulation, ultimately promoting apoptosis and ferroptosis. Consistently, both compounds decreased Δψm, induced MPTP opening, and disrupted redox homeostasis, as evidenced by reduced antioxidant enzyme activities and GSH depletion. Mechanistically, PFOA and PFOS activated mitochondrial-mediated apoptosis, indicated by BAX upregulation, BCL2 downregulation, Caspase 3 activation, and PARP1 cleavage. Meanwhile, ferroptosis was triggered, as shown by increased intracellular iron and MDA accumulation, GPX4 downregulation, and ACSL4 upregulation. In conclusion, PFOA and PFOS impair human sperm capacitation by inducing mitochondrial-mediated apoptosis and ferroptosis, thereby compromising fertilization potential. These findings provide novel mechanistic insights into PFAS-induced male reproductive toxicity.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"309 ","pages":"Article 119743"},"PeriodicalIF":6.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145972835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Source analysis and Monte Carlo-based risk assessment of groundwater heavy metal contamination in typical industrial regions of Jiangxi, China","authors":"Xin Ke,&nbsp;Xinping Xiao,&nbsp;Qiang Chen,&nbsp;Jiusheng Ren,&nbsp;Yuanyuan Pan","doi":"10.1016/j.ecoenv.2026.119728","DOIUrl":"10.1016/j.ecoenv.2026.119728","url":null,"abstract":"<div><div>Groundwater is a crucial water resource that underpins human survival and industrial and agricultural development. The pollution levels and health risks of heavy metals in the groundwater have garnered substantial attention. This study investigated the pollution characteristics, sources, and ecological and health risks of heavy metals in the groundwater of typical industrial areas. The Nemerow integrated pollution indexes showed that 86 % groundwater samples in industrial areas were contaminated with heavy metals when referencing the WHO drinking water guidelines. The distribution of heavy metals exhibited significant spatial heterogeneity, as evidenced by the high coefficient of variation. Principal component analysis showed that water-rock interaction and industrial point-source pollution might be the primary contributors to these heavy metals in groundwater. Among these groundwater samples, 17.24 % of samples presented mild or higher ecological risks. Besides, both adults and children were in danger of health risk. Arsenic (As, 57.38 %), Mn (29.68 %) and Pb (10.86 %) were the predominant contributors to the unacceptable non-carcinogenic risk, while As (50.32 %) and Ni (49.14 %) were responsible for the carcinogenic risk, respectively. This study helps to reveal the pollution patterns and sources of heavy metals in the groundwater of industrial areas, and provides a theoretical basis for management measures against pollution.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"309 ","pages":"Article 119728"},"PeriodicalIF":6.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145972996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pentose phosphate pathway regulates oxidative damage and apoptosis of chondrocytes induced by fluoride","authors":"Fang-fang Yu ,&nbsp;Huan-xia Zhang ,&nbsp;Kang-ting Luo ,&nbsp;Shui-yuan Yu ,&nbsp;Gao-wa Naren ,&nbsp;Miao Wang ,&nbsp;Juan Zuo ,&nbsp;Qian Li ,&nbsp;Tong-tong Sha ,&nbsp;Zai-chao Dong ,&nbsp;Qian Zhang ,&nbsp;Guo-yu Zhou ,&nbsp;Zhi-guang Ping ,&nbsp;Cui-yan Wu ,&nbsp;Yue Ba","doi":"10.1016/j.ecoenv.2025.119665","DOIUrl":"10.1016/j.ecoenv.2025.119665","url":null,"abstract":"<div><div>Fluorosis is a systemic disorder with primary manifestations including skeletal and dental fluorosis, where skeletal fluorosis is associated with cartilage lesions. This study investigated the pentose phosphate pathway (PPP) regulated chondrocyte apoptosis and oxidative damage induced by fluoride. Bioinformatics analysis of Gene Expression Omnibus dataset (GSE70719) showed that PPP was significantly enriched in fluorine-induced osteocytes damage. We confirmed that sodium fluoride (NaF) inhibited the PPP of chondrocytes, decreased the nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH) levels, and enhanced apoptosis and oxidative injury. Moreover, NaF significantly inhibited the PPP and promoted apoptosis in rat articular cartilage. AG1, an agonist of the key enzyme glucose-6-phosphate dehydrogenase in PPP, significantly increased PPP, alleviated chondrocyte apoptosis and oxidative damage induced by NaF. These results confirmed that NaF inhibited the PPP, reduced NADPH and GSH levels, and increased oxidative stress, ultimately leading to oxidative damage and apoptosis in chondrocytes. AG1 alleviated apoptosis and oxidative damage in NaF-induced chondrocytes by activating PPP.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"309 ","pages":"Article 119665"},"PeriodicalIF":6.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomic mechanisms of phytoremediation in petroleum-contaminated soil assisted by the combined application of microbial agent and biochar","authors":"Xin Fang ,&nbsp;Pufan Zheng ,&nbsp;Kefan Wang ,&nbsp;Yiping Lin ,&nbsp;Zilu Wang ,&nbsp;Nuo Li ,&nbsp;Cong Shi ,&nbsp;Fuchen Shi","doi":"10.1016/j.ecoenv.2025.119647","DOIUrl":"10.1016/j.ecoenv.2025.119647","url":null,"abstract":"<div><div>Petroleum contamination poses a serious threat to soil ecosystems, demanding effective and green remediation solutions. This study developed a kind of synergistic strategy combining the plant <em>Tagetes erecta</em> with microbial agent and biochar for treating petroleum-contaminated soil. After a 90-day remediation period, the combined treatment achieved a total petroleum hydrocarbon degradation rate of 76.6 % and reduced all 16 priority polycyclic aromatic hydrocarbons below detection limits. Metabolomic analysis identified 1022 metabolites and revealed significant differences in metabolic profiles, both between rhizosphere and nonrhizosphere soils and between the combined treatment and plant‑only treatment. KEGG pathway and key metabolite analyses revealed that treatments with the microbial agent upregulated the nonribosomal peptide structures pathway and the associated metabolite surfactin. This finding suggests a potential enhancement of biosurfactant-mediated hydrocarbon emulsification. Metabolic pathways related to plant-microbe interactions, such as eicosanoid and arachidonic acid metabolism, were also enriched. Furthermore, the levels of antibacterial metabolites like 3,6-diiodo-9H-carbazole showed decrease in the soil, whereas the levels of plant auxin precursor indole-3-butyric acid increased. These results demonstrate that the remediation approach used in this study can enhance petroleum contaminant degradation by modulating the soil metabolic network and strengthening biological interactions. This strategy dissects the differential metabolic responses under the combined plant-microbe-biochar remediation, providing new insights for the green and sustainable remediation of petroleum-contaminated soil.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"309 ","pages":"Article 119647"},"PeriodicalIF":6.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Icaritin alleviates UVB-induced skin damage by inhibiting ferroptosis via modulation of mitochondrial dynamics","authors":"Wenru Zhi ,&nbsp;Ying Zheng ,&nbsp;Dandan Gou ,&nbsp;Lu Guo ,&nbsp;Yuheng Li ,&nbsp;Hefei Huang ,&nbsp;Mingcheng Du ,&nbsp;Dianmei Yu ,&nbsp;Keming Lu ,&nbsp;Jin’e Wang ,&nbsp;Zhiyong Zhou","doi":"10.1016/j.ecoenv.2025.119625","DOIUrl":"10.1016/j.ecoenv.2025.119625","url":null,"abstract":"<div><div>Ultraviolet B (UVB) radiation is the main environmental cause of skin damage, and ferroptosis plays a crucial role in its damage process. This study investigated the protective effects and mechanisms of icaritin (ICT) against UVB-induced skin injury. Our results showed that ICT significantly alleviated UVB-induced cutaneous dryness, erythema, and epidermal hyperplasia in mice, while increasing collagen fiber content. In vitro, ICT restored the viability of UVB-exposed L929 fibroblasts. Meanwhile, ICT significantly inhibited ferroptosis in fibroblasts, manifested by downregulation of COX2, upregulation of GPX4 and FTH1, and reduction of lipid ROS and lipid peroxidation levels. Further investigation revealed that, ICT ameliorated mitochondrial dysfunction by restoring membrane potential, enhancing ATP production, decreasing ROS, and normalizing the NAD+ /NADH ratio. Morphological and protein analysis confirmed that ICT improves mitochondrial homeostasis by regulating mitochondrial dynamics, thereby inhibiting ferroptosis. These findings confirmed that ICT as a promising therapeutic agent for UVB-induced skin damage.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"309 ","pages":"Article 119625"},"PeriodicalIF":6.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects and mechanisms of sodium arsenite exposure on liver injury in mice","authors":"Kaiyan Shen ,&nbsp;Zuoshun He ,&nbsp;Shunrong Ma ,&nbsp;Bo Zhao ,&nbsp;Jiamin Yuan ,&nbsp;Sina Yang ,&nbsp;Yanying Hu ,&nbsp;Ning Xu ,&nbsp;Shiyan Gu","doi":"10.1016/j.ecoenv.2025.119624","DOIUrl":"10.1016/j.ecoenv.2025.119624","url":null,"abstract":"<div><div>As a common environmental pollutant, chronic exposure to arsenic can cause liver damage, however the molecular mechanisms remain unclear. This study investigates explore the liver toxicity induced by NaAsO₂ exposure in mice, focusing on molecular mechanisms and potential therapeutic targets. Male C57BL/6 J mice were treated with NaAsO₂ at 3, 6, and 12 mg/kg doses for 4 weeks. Body weight, liver index, serum ALT/AST levels, oxidative stress markers (MDA, SOD, GPx), histopathological changes, and apoptotic were assessed. RNA sequencing was used to identified differentially expressed genes (DEGs) and protein-protein interaction (PPI) network was further established to elucidate the interactions among the potential targets. Significant liver damage was observed at 6 mg/kg and 12 mg/kg doses, with the 12 mg/kg group showing elevated serum ALT (39.34 ± 1.21 U/L) and AST (200.79 ± 9.73 U/L). At those doses, oxidative stress markers were significantly altered and histology revealed hepatocyte disarrangement, vacuolation, and necrosis, and the TUNEL assay further conformed significant apoptosis. In the livers of treated mice, transcriptomic analysis identified 149 DEGs at 6 mg/kg and 259 DEGs at 12 mg/kg. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated disruptions in circadian rhythm, lipid metabolism, and immune signaling pathways. More importantly, <em>Il1b</em>, <em>Acta2</em>, and <em>Serpine1</em> were identified as key regulatory genes, showing elevated expression. In conclusion, these findings indicate that NaAsO₂ exposure disrupts metabolic, circadian, and immune pathways, with inflammation being exacerbated at higher doses. <em>Il1b</em>, <em>Acta2</em>, and <em>Serpine1</em> emerge as promising therapeutic targets for arsenic-induced liver damage. Future research should focus on long-term interventions and drug repurposing strategies to validate these targets and mitigate arsenic toxicity.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"309 ","pages":"Article 119624"},"PeriodicalIF":6.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developmental perfluorooctane sulfonate (PFOS) exposure alters gene expression in nucleus accumbens and prefrontal cortex and impairs cognition in rats: A transcriptomic and mediation analysis","authors":"Shiwen Li ,&nbsp;Hongxu Wang ,&nbsp;Ana C. Maretti-Mira ,&nbsp;Tomas K. D. Manea ,&nbsp;Shaun Y. Kim ,&nbsp;Lida Chatzi ,&nbsp;Jesse A. Goodrich ,&nbsp;Tanya L. Alderete ,&nbsp;Nathan Young ,&nbsp;Ruth I. Wood ,&nbsp;Max T. Aung","doi":"10.1016/j.ecoenv.2025.119648","DOIUrl":"10.1016/j.ecoenv.2025.119648","url":null,"abstract":"<div><div>Growing evidence suggests that developmental exposure to perfluorooctanesulfonic acid (PFOS) is linked to neurobehavioral outcomes. Pregnant female rats were exposed to PFOS (15 mg/L) or Tween vehicle through drinking water until the offspring were weaned at three weeks of age. As adults, cognitive flexibility and impulsive decision-making were assessed in 8 PFOS-exposed and 8 vehicle-exposed rats using extradimensional set-shifting and delay discounting tasks, respectively. Cognitive flexibility was measured by the number of trials required to reach the criterion, while impulsive decision-making was quantified as the area under the curve (AUC) of the percent preference for the large reward lever (% CHL), response omissions (% omit), and response latency (in second) at delays of 0, 15, 30, and 45 s. Brain tissues from the nucleus accumbens, prefrontal cortex, and hippocampus were extracted for bulk RNA sequencing. Differential gene expression analysis and gene set enrichment analysis were performed. Mediation analysis was performed to assess the mediated effect of DEGs in the associations between PFOS and neurobehavioral tests. We identified 62 differentially expressed genes (DEGs) in the nucleus accumbens, 34 in the hippocampus, and 59 in prefrontal cortex tissues due to PFOS exposure. We also found DEGs, including <em>NAT8F2</em>, <em>AC080157.1</em>, <em>ABCG3</em>, and <em>ENSRNOG00000063145</em> mediated between PFOS and neurobehavioral assessments. Pathways that were associated with both PFOS exposure and neurobehavioral outcomes (% CHL and % omit) included extracellular matrix-receptor interaction, focal adhesion, and glutathione metabolism in the nucleus accumbens. Developmental PFOS exposure may alter gene expression in the nucleus accumbens and prefrontal cortex and was associated with impaired cognitive flexibility and impulsive decision-making. These exploratory findings highlight potential pathways, including ECM-receptor interaction and glutathione metabolism, that warrant further validation.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"309 ","pages":"Article 119648"},"PeriodicalIF":6.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}