Food and Chemical Toxicology最新文献

{"title":"Dioxin and PCB monitoring in Greek food products during the period 2002–2022 and preliminary assessment of general population exposure through the diet","authors":"Danae Costopoulou,&nbsp;Irene Vassiliadou,&nbsp;Kleopatra Kedikoglou,&nbsp;Constantina Grigoriou,&nbsp;Leondios Leondiadis","doi":"10.1016/j.fct.2025.115717","DOIUrl":"10.1016/j.fct.2025.115717","url":null,"abstract":"<div><div>Human dietary exposure to polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), dioxin-like polychlorinated biphenyls (DL-PCBs) and non dioxin-like polychlorinated biphenyls (NDL-PCBs) is of worldwide scientific concern due to the health hazards associated with these compounds. In this study an estimation of the dietary intake of adolescents and adults in Greece was attempted for the first time. Representative samples from food categories widely consumed in Greece were collected and analyzed during a period of 21 years (2002–2022). Occurrence data found were combined with food consumption data available in the EFSA Comprehensive Food Consumption Database, to assess the dietary exposure of the Greek population. The food group with the highest total (PCDD/Fs and DL-PCBs) mean upperbound concentration was “fish and seafood” with 0.71 pg WHO-TEQ g⁻¹ wet weight (ww) (9.68 pg WHO-TEQ g⁻¹ fat) and the one with the lowest mean WHO-TEQ concentration was the “vegetable oil” group, 0.35 pg WHO-TEQ g⁻¹ fat. The highest amounts of indicator PCBs (ind-PCBs), were detected in the “fish and seafood’’ category (5.25 ng g⁻¹ ww, 86.8 ng g⁻¹ fat) whereas the lowest mean concentration was found in eggs (1.56 ng g⁻¹ fat). For adult Greek population the average daily intake in PCDD/Fs and DL-PCBs is 1.02 pg WHO-TEQ kg body weight⁻¹ (bw), which corresponds to 7.14 pg WHO-TEQ kg bw⁻¹ weekly intake whereas the average daily intake in ind.-PCBs is 5.51 ng kg bw⁻¹. The main contributor to the total dietary intake in PCDD/Fs and PCBs is the “fish and seafood” category. The general background dietary exposure of the Greek population to PCDD/Fs and DL-PCBs estimated is within the tolerable daily intake (TDI) value range of 1–4 pg WHO-TEQ kg bw ⁻¹ proposed by the WHO in 1998, but exceeds the tolerable weekly intake (TWI) of 2 pg WHO-TEQ kg bw⁻¹ proposed in the updated scientific opinion of the EFSA CONTAM Panel in 2018.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"206 ","pages":"Article 115717"},"PeriodicalIF":3.5,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PFOS promotes lung adenocarcinoma cell proliferation through PI3K/AKT/NF-κB mediated EMT","authors":"Ruijian Liu ,&nbsp;Qiuyu Yang ,&nbsp;Shanshan Fan ,&nbsp;Yifeng He ,&nbsp;Juan Duan ,&nbsp;Shengming Zhang ,&nbsp;Haowei Xiong ,&nbsp;Deqin Zeng","doi":"10.1016/j.fct.2025.115714","DOIUrl":"10.1016/j.fct.2025.115714","url":null,"abstract":"<div><div>Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are synthetic chemicals widely used in consumer and industrial sectors, with PFOS being particularly notable for its extensive applications. However, PFOS exposure has been associated with health issues, and while its biotoxicity—especially carcinogenic effects—has been documented, the specific risks and mechanisms in lung cancer remain unclear. This study investigates the effects of PFOS on lung adenocarcinoma (LUAD) cell lines and elucidates its carcinogenic mechanisms. We evaluated PFOS-induced proliferation in H1299 and A549 LUAD cells, focusing on its anti-apoptotic properties and impact on epithelial-mesenchymal transition (EMT), while also examining activation of the PI3K/AKT/NF-κB pathway and its role in apoptosis inhibition. Results show PFOS significantly promotes H1299 and A549 cell growth via anti-apoptotic effects, accelerates EMT in LUAD cells to enhance migration, and activates the PI3K/AKT/NF-κB pathway to facilitate proliferation and migration. These findings suggest PFOS exposure may exacerbate pre-existing lung conditions or induce carcinogenesis by suppressing apoptosis and activating PI3K/AKT/NF-κB signaling, providing evidence for PFOS-related carcinogenic potential in LUAD.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"205 ","pages":"Article 115714"},"PeriodicalIF":3.5,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144907060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ligand- and tissue-specific differences in the activation of the aryl hydrocarbon receptor by flavonoids: A focus on baicalein and scutellarein","authors":"Tong Xu ,&nbsp;Yiyun Liu ,&nbsp;Fang Han ,&nbsp;Heidi Qunhui Xie ,&nbsp;Guanglei Yang ,&nbsp;Ruoyu Wang ,&nbsp;Li Xu","doi":"10.1016/j.fct.2025.115713","DOIUrl":"10.1016/j.fct.2025.115713","url":null,"abstract":"<div><div>Flavonoids are natural dietary modulators of the aryl hydrocarbon receptor (AHR) with considerable therapeutic potential. However, their safety and efficacy remain difficult to predict due to the complex, ligand- and tissue-specific differences of AHR. In this study, we combined transcriptional and protein-level experiments with computational methods, including molecular docking and R-based RNA-seq analyses, to elucidate the patterns of cell type-specific activation of AHR by structurally similar flavonoids. Among six tested flavonoids, baicalein (Ba) and scutellarein (Sc) were the most potent AHR activators based on a bio-detection system and were further confirmed as potential AHR ligands through molecular docking. Mechanistic studies revealed that Ba significantly increased CYP1A1 expression in HepG2 cells and CYP1B1 expression in U87 cells through the AHR pathway. Interestingly, Sc induced AHR-dependent CYP1B1 expression in U87 cells but exerted partial AHR-dependent effects on CYP1A1 expression in HepG2 cells. These findings highlight cell type-specific regulatory patterns that may reflect tissue-specific regulation of the AHR pathway induced by structurally similar flavonoids, contributing to providing further mechanistic insights into their toxicological and pharmacological properties. Overall, this work offers a scientific basis for the development and safety assessment of flavonoid-based nutraceuticals and therapeutic agents.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"205 ","pages":"Article 115713"},"PeriodicalIF":3.5,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144903880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developmental toxicity and gene expression alterations induced by the synthetic cannabinoid CUMYL-4CN-BINACA in zebrafish embryos","authors":"Derya Yılmaztürk ,&nbsp;Ömercan Alat ,&nbsp;Özkan Aksakal ,&nbsp;Berşan Kullebi ,&nbsp;Ayşe Lafzi ,&nbsp;Turgay Şişman","doi":"10.1016/j.fct.2025.115712","DOIUrl":"10.1016/j.fct.2025.115712","url":null,"abstract":"<div><div>Synthetic cannabinoids like CUMYL-4CN-BINACA are emerging psychoactive substances with largely unknown developmental toxicity. Given the growing concern about prenatal and early-life exposure, this study assessed its impact on zebrafish embryos, focusing on morphological development, larval behavior, and gene expression. Embryos were exposed to concentrations of 1.25–40.0 mg/L during short-term (3–24 hpf) and long-term (3–120 hpf) windows. Key developmental endpoints, including survival, heartbeat, hatching, and locomotor activity, were evaluated. Molecular analyses were performed using qPCR to assess the expression of 19 genes related to apoptosis, behavior, and neurotransmission. Short-term exposure did not produce significant morphological changes, while long-term exposure resulted in concentration-dependent teratogenic effects such as pericardial and yolk sac edema, axial deformities, and hypoactivity. The LC₅₀ and EC₅₀ at 120 hpf were calculated as 16.624 mg/L and 9.083 mg/L, respectively. Gene expression analysis revealed significant alterations in behavioral genes (<em>gnrh3, gnrhr3, kiss2</em>), apoptotic markers (<em>casp3a, casp8, ifng1, tp53</em>), and the DNA repair gene <em>rad51</em>. Neurotransmission-related genes in dopaminergic (<em>dat, drd1, drd3</em>), serotonergic (<em>5ht1aa, 5ht1a, 5ht1b, 5ht2c</em>), and GABAergic (<em>gabra1, gat1, abat, gad1b</em>) systems were also dysregulated. These findings highlight the developmental and neurotoxic potential of CUMYL-4CN-BINACA, underlining the need for further toxicological risk assessments in early vertebrate models.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"205 ","pages":"Article 115712"},"PeriodicalIF":3.5,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144907059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human exposure to persistent organic pollutants in Switzerland: The role of diet, age, smoking, and body composition","authors":"C. Oltramare ,&nbsp;J. Riou ,&nbsp;M. Bochud ,&nbsp;M. Zennegg ,&nbsp;D. Vernez ,&nbsp;A. Berthet","doi":"10.1016/j.fct.2025.115711","DOIUrl":"10.1016/j.fct.2025.115711","url":null,"abstract":"<div><div>Persistent organic pollutants (POPs), including polychlorinated dibenzo-p-dioxin/dibenzofuran (PCDD/Fs) and polychlorinated biphenyls (PCBs), are widespread environmental contaminants that bioaccumulate in human, primarily through dietary intake. We conducted a cross-sectional study performed in Lausanne, Switzerland to investigate the association between the serum concentrations of POPs and individual characteristics. We measured 17 PCDD/Fs, 12 dl-PCBs and 6 i-PCBs in 80 volunteers. Participants provided demographic and lifestyle data and completed a food frequency questionnaire. Geometric mean concentrations were 6.2 pgTEQ/g lipid for PCDD/Fs, 4.2 pgTEQ/g lipid for dl-PCBs and 117.3 ng/g lipid for i-PCBs. Age, body fat mass, smoking status were statistically associated with serum concentrations. Dietary associations were congener-specific; notably, egg consumption correlated with higher PCDF concentrations, and plant-based foods were, unexpectedly, linked to increased overall POP levels. Active smoking was associated with higher PCB serum concentrations. We highlighted divergent association (smoking status or body fat mass) between PCDD/Fs and PCBs although they share similar physico-chemical properties. The ubiquity of pollutants in the environment has led to their widespread presence in human body, despite stringent regulation. There is an urgent need to investigate the food contamination origin to reduce the general population exposure to environmental pollutants.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"205 ","pages":"Article 115711"},"PeriodicalIF":3.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144903879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aristolochic acid I promotes renal tubulointerstitial fibrosis by activating the mannan-binding lectin serine protease 1-complement system","authors":"Chen Wang ,&nbsp;Hong Zhang ,&nbsp;Jiahe Wang ,&nbsp;Huimin Wu ,&nbsp;Jing Ye ,&nbsp;Qi Zhang ,&nbsp;Baoping Jiang ,&nbsp;Langqun Chen ,&nbsp;Ying Wang ,&nbsp;Siyu Cheng ,&nbsp;Jiahui Ying ,&nbsp;Yujie Xiang ,&nbsp;Yiran Cheng ,&nbsp;Liang Zhang","doi":"10.1016/j.fct.2025.115708","DOIUrl":"10.1016/j.fct.2025.115708","url":null,"abstract":"<div><div>Aristolochic acid I (AAI) activates the complement system, triggering inflammation and renal interstitial fibrosis (RIF). This study investigated the role of mannan-binding lectin serine protease 1 (MASP1) in AAI-induced RIF. Treating human proximal tubular (HK-2) cells with AAI (2.5, 5, 10 μM) increased inflammatory factors, fibrosis proteins, complement factor C3a, and MASP1/MASP2 expression. Similar increases occurred in AAI-treated (5 mg/kg) C57BL/6J mice. Inhibiting MASP1 using siRNA (siMASP1) or an inhibitor (C1INH, 100 μg/mL) in HK-2 cells reduced AAI-induced C3a elevation, complement activation, inflammation, MASP2, and fibrosis proteins. Correspondingly, in situ renal inhibition of MASP1 in mice using adeno-associated virus 9 (AAV9-siMASP1) suppressed complement activation, kidney inflammation, and RIF following AAI exposure. These results demonstrate that AAI promotes RIF by activating the MASP1-complement pathway, leading to C3a release and inflammation. This study elucidates a mechanism for AAI-induced RIF and suggests MASP1 inhibition as a potential therapeutic strategy against AAI toxicity.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"205 ","pages":"Article 115708"},"PeriodicalIF":3.5,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144907056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consumption of fermented Cd and Pb contaminated wheat flour increases potential health risk","authors":"Weiqin Xing ,&nbsp;Zhexu Si ,&nbsp;James A. Ippolito ,&nbsp;Guobing Lin ,&nbsp;Farzana Kastury ,&nbsp;Sen Ma ,&nbsp;Kunyan Qiu ,&nbsp;Linlin Zhao ,&nbsp;Lena Q. Ma ,&nbsp;Liping Li","doi":"10.1016/j.fct.2025.115710","DOIUrl":"10.1016/j.fct.2025.115710","url":null,"abstract":"<div><div>Fermentation can increase the availability of heavy metals in wheat flour, however, its effect on the health risk of heavy metal contaminated wheat flour has not been fully investigated. A contaminated wheat flour (Pb = 0.26, Cd = 0.35 mg kg⁻¹) was fermented with yeast at 30 °C for 1 h, made into mantou and fed to mice for 14 days; a control without fermentation was also utilized. The mouse organ/tissue and feces were analyzed for Pb, Cd, Cu, Mn, Ni and Zn concentrations, and phytate concentrations of the fermented and unfermented wheat flour were also measured. Results indicated that mice fed contaminated fermented flour had 100 % greater liver and kidney Cd concentrations, and significantly greater liver Zn (9.40 %), kidney Pb (40.3 %) and Ni concentrations (40.6 %) than mice fed contaminated unfermented flour. Cadmium relative bioavailability of the contaminated fermented flour was 100 % greater than that in the contaminated unfermented flour. Thirteen days post-metal exposure, significantly lower Cd and Mn concentrations were found in feces from mice fed contaminated fermented flour than unfermented flour. Overall, results suggest a potential increased health risk of Pb and Cd contaminated wheat flour consumption following fermentation.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"205 ","pages":"Article 115710"},"PeriodicalIF":3.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144895771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional evaluation of fibroblast-to-myofibroblast transition as an in vitro screening tool for pulmonary fibrosis","authors":"Min Ju Kim ,&nbsp;Su Bin Park ,&nbsp;Hee-Sung Hwang ,&nbsp;Chunghyun Kim ,&nbsp;Juhee Lee ,&nbsp;Seung Min Oh","doi":"10.1016/j.fct.2025.115705","DOIUrl":"10.1016/j.fct.2025.115705","url":null,"abstract":"<div><div>Polyhexamethylene guanidine (PHMG), a major component of humidifier disinfectants (HDs) linked to fatal lung injuries, has been implicated in the development of pulmonary fibrosis. However, most previous studies have primarily focused on epithelial injury, with limited attention to fibroblast activation - a central mechanism in fibrogenesis.</div><div>In this study, we present an integrated testing strategy (ITS) designed for the early in vitro screening of fibrogenic agents, centered on fibroblast-to-myofibroblast transition (FMT) as a core functional and mechanistic endpoint. Human lung fibroblasts (MRC-5) were exposed to PHMG-HCl, and fibrotic responses were assessed across four key events (KEs): (1) TGF-β1 signaling activation, (2) myofibroblast differentiation, (3) extracellular matrix (ECM) deposition, and (4) enhanced cell migration and contraction.</div><div>PHMG-HCl exposure led to increased reactive oxygen species (ROS) generation and upregulation of TGF-β1, α-SMA, and COL1A, consistent with FMT induction. Functional assays further demonstrated elevated cell motility and collagen gel contraction. These in vitro finding were corroborated by in vivo rat models and 3D EpiAirway™ systems, which exhibited inflammation, collagen deposition, and epithelial barrier disruption.</div><div>Collectively, this FMT-based ITS provides a mechanistically grounded and functionally predictive platform for early identification of pulmonary fibrogenic potential, offering an efficient and ethical alternative to traditional toxicity testing methods.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"205 ","pages":"Article 115705"},"PeriodicalIF":3.5,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144907057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polystyrene nanoplastics impair endometrial decidualization via cell cycle arrest and JNK-MAPK pathway-mediated oxidative stress in early pregnant mice","authors":"Jing-Ai Li ,&nbsp;Li-Qing Wang ,&nbsp;Qiong-Jun Xu ,&nbsp;Xiao-Mei Wu ,&nbsp;Xiao-Qing Pang ,&nbsp;Jin-Xin He ,&nbsp;Qian-Feng Qiao ,&nbsp;Huang-Nian You ,&nbsp;Yan-Chun Wu ,&nbsp;Yong-Jiang Zhou","doi":"10.1016/j.fct.2025.115707","DOIUrl":"10.1016/j.fct.2025.115707","url":null,"abstract":"<div><div>The ubiquitous polystyrene nanoplastics (PS-NPs) in the environment have emerged as a significant public health concern. Their biological safety, particularly their impact on female fertility, has garnered increasing attention. Our previous study demonstrated that PS-NPs impaired endometrial decidualization. However, the underlying mechanism remains unclear. In this study, we explored the underlying mechanism by which PS-NPs compromised decidualization in early pregnant mice. Our results showed that PS-NPs disrupted uterine decidualization. Specifically, PS-NPs inhibited endometrial cell proliferation and hindered the formation of decidual polyploid cells. Additionally, PS-NPs induced oxidative damage in uteri by disrupting the balance between oxidative stress and antioxidative defenses in the decidua. PS-NPs interfered with the formation of CyclinD1-Cdk4, CyclinE1-Cdk2, CyclinA1-Cdk2, and CyclinB1-Cdk1 complexes, ultimately impairing cell cycle progression at the G1-S and G2-M phases. Inhibition of the JNK-MAPK pathway alleviated excessive oxidative stress in uteri, restored defective decidualization, and improved embryo implantation in PS-NPs-exposed pregnant mice. Further analysis revealed that the JNK-MAPK pathway mediated the PS-NPs-induced suppression of endometrial proliferation. These findings suggested that impaired endometrial proliferation driven by reduced activity of CyclinD1-Cdk4, CyclinE1-Cdk2, CyclinA1-Cdk2, and CyclinB1-Cdk1 complexes may be an important contributor to PS-NPs-induced decidualization defect. Moreover, the JNK-MAPK pathways may be mediators of these detrimental effects.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"205 ","pages":"Article 115707"},"PeriodicalIF":3.5,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144866714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pesticide-induced epigenetic suppression of WNT signaling and NF-κB-driven inflammation impairs ovarian function in rats","authors":"Jasmeena Jan ,&nbsp;Wajid Mohammad Sheikh ,&nbsp;Shazia Gul ,&nbsp;Rumaisa Mohidin ,&nbsp;Owais Mohmad Bhat ,&nbsp;Mohammad Nadeem Lone ,&nbsp;Showkat Ahmad Shah ,&nbsp;Abid Hamid Dar ,&nbsp;Mohammad Afzal Zargar ,&nbsp;Showkeen Muzamil Bashir ,&nbsp;Nissar Ahmad Wani","doi":"10.1016/j.fct.2025.115706","DOIUrl":"10.1016/j.fct.2025.115706","url":null,"abstract":"<div><div>The study examined the impact of chlorpyrifos, dimethoate, and their co-exposure on ovarian structure and function in female Wistar rats. The study involved 24 rats, divided into four groups: control, chlorpyrifos (3 mg/kg), dimethoate (30 mg/kg), and combination. Histopathology revealed degenerated and atretic follicles, disorganized granulosa cells and cystic follicles in pesticide exposed rats. Hormonal analysis showed decrease in FSH, LH, PG, T and AMH and increase in ED levels. Gene expression studies revealed significant upregulation of <em>ESR2</em> (∼2, ∼1.8, and ∼1.85 fold respectively) in chlorpyrifos, dimethoate and combination groups. In contrast, <em>RSPO2, WNT7A, WNT3A</em> and <em>WNT5A</em> were downregulated (reduced by ∼1.73–1.8, 1.7–2.6, 1.45–2.13 and 1.3–1.75 fold, respectively). The changes correlated with reduced <em>β-catenin</em> activation. DNA methylation analysis revealed an inverse correlation between methylation and gene expression, alongside upregulation of <em>DNMT3A</em> and <em>DNMT3B</em> (∼4.5, ∼2.1, ∼4.9; ∼3.75, ∼2.2, ∼3.8 fold in chlorpyrifos, dimethoate and combination groups respectively), suggesting methylation-mediated repression. Furthermore, enhanced expression of inflammation-related genes and cytokines, coupled with <em>NF-κB</em> activation, indicated significant inflammatory responses. Overall, the findings highlight gene specific DNA methylation and inflammatory disruptions in pesticide-exposed ovaries. However, the lack of ChIP assay limits confirmation of <em>DNMT</em> recruitment, which should be addressed in future studies.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"205 ","pages":"Article 115706"},"PeriodicalIF":3.5,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}