Particle and Fibre Toxicology最新文献

{"title":"Ultraviolet irradiation-induced enhancement of inflammatory potential of polystyrene nano- and microplastics and effects of dispersion on lung clearance.","authors":"Yeonjeong Ha, Jun Hui Jeon, Eunsol Bae, Songyeon Kim, Gyuri Kim, Soyeon Jeon, So-Young An, Hyeong-Gyu Lim, Sung Ik Yang, Wan-Seob Cho","doi":"10.1186/s12989-026-00680-x","DOIUrl":"https://doi.org/10.1186/s12989-026-00680-x","url":null,"abstract":"<p><strong>Background: </strong>Microplastics are pervasive environmental pollutants that pose potential risks to human health, particularly through inhalation. Despite growing concerns, limited data exist on how environmental aging, such as ultraviolet (UV) irradiation, affects the pulmonary toxicity of inhaled nano- and microplastics. This study evaluated the influence of UV-driven surface oxidation on the inflammatory potential and lung clearance kinetics of polystyrene (PS) particles. Spherical PS particles (50, 200, and 400 nm) were synthesized, selectively oxidized by UV irradiation, and thoroughly characterized for surface chemistry and intrinsic reactive oxygen species (ROS) generation.</p><p><strong>Results: </strong>Mice exposed to these particles via pharyngeal aspiration (75 µg/mouse; n = 4 per group) exhibited significantly greater acute pulmonary inflammation from UV-oxidized particles compared to pristine particles, with smaller ones (50 nm) displaying slightly higher inflammogenicity. Although inflammation largely resolved by four weeks post-exposure (75 µg/mouse; n = 4 per group), mild neutrophilic inflammation persisted. Notably, particle-induced ROS generation and subsequent cellular oxidative stress in alveolar macrophages showed strong correlations with acute inflammatory endpoints. Additionally, the particle dispersion method significantly affected lung clearance rates: particles dispersed in distilled water (DW) containing 10% ethanol exhibited shorter clearance half-lives (3-8 days) than those dispersed in 5% mouse serum (~ 18 days) (75 µg/mouse; n = 4 per group). These results highlight the dispersion medium as an important experimental variable influencing pulmonary clearance and toxicity interpretation.</p><p><strong>Conclusions: </strong>These findings suggest that the surface oxidation of nano- and microplastics through environmental aging can increase associated health risks. However, within the tested size range (50-400 nm), neither surface oxidation nor particle size markedly altered the overall lung clearance pattern.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polystyrene microplastics and hepatic fibrosis-related indices in type 2 diabetes: a cross-sectional analysis with experimental validation.","authors":"Ying Sun, Xiaoqin Xu, Guoting Sun, Jiang Li, Bowei Yu, Yuying Wang, Kun Zhang, Fangzhen Xia, Yingli Lu, Ningjian Wang","doi":"10.1186/s12989-026-00681-w","DOIUrl":"https://doi.org/10.1186/s12989-026-00681-w","url":null,"abstract":"<p><strong>Background: </strong>Microplastics (MPs) are emerging environmental contaminants with potential hepatotoxicity, yet direct epidemiological evidence linking internal MP exposure to liver injury is scarce, particularly in individuals with type 2 diabetes (T2D). In this cross-sectional study nested within the METAL2 cohort, we aimed to characterize blood microplastic profiles in patients with T2D and to determine whether specific MP polymers are associated with hepatic steatosis and fibrosis risk, with experimental validation of the identified polymer.</p><p><strong>Results: </strong>In patients with T2D, multiple MP polymers were detectable in blood, with polyvinyl chloride (PVC), polyamide 66 (PA66), and polystyrene (PS) being the most prevalent. Although PVC constituted the largest proportion of total MP burden, PS showed the most consistent nominal positive liver-related signal in the human analyses, including higher levels in participants with elevated fibrosis risk and higher FIB-4 and ALT in the highest exposure quartile. Experimental validation in diabetic mice demonstrated that PS microplastics markedly exacerbated hepatic steatosis, inflammation, and collagen deposition, leading to overt liver fibrosis. Mechanistically, PS-MPs exposure disrupted hepatic lipid homeostasis and concurrently activated the NLRP3 inflammasome and the TGF-β1/Smad signaling pathway, promoting inflammatory amplification and hepatic stellate cell activation.</p><p><strong>Conclusion: </strong>This integrated human and experimental study provides preliminary evidence that circulating PS-associated signals are linked to liver-related indices in T2D, while experimental findings support the biological plausibility that PS exposure may aggravate hepatic injury under diabetic conditions.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epithelial NLRP3 drives silica-induced lung injury and fibrosis through IL-18 and pro-fibrotic neutrophil recruitment.","authors":"Maggie Lam, Kristian T Barry, Christopher J Hodges, Alison C West, Christopher M Harpur, Ashley Mansell, Michelle D Tate","doi":"10.1186/s12989-026-00682-9","DOIUrl":"https://doi.org/10.1186/s12989-026-00682-9","url":null,"abstract":"<p><strong>Background: </strong>Silicosis is a progressive inflammatory and fibrotic lung disease with no effective treatments beyond symptom management. While global NLRP3 inflammasome deficiency attenuates silica-induced pathology, myeloid-specific Nlrp3 deletion provides no protection, suggesting that other cellular sources drive disease. Given that epithelial cells directly encounter inhaled silica particles and express NLRP3, we investigated the functional contribution of epithelial Nlrp3 to silicosis pathogenesis.</p><p><strong>Results: </strong>Using inducible epithelial-specific knockout models, we found that alveolar epithelial (Sftpc⁺) cells drive early caspase-1 activation and airway IL-18 production, while partially reducing tissue IL-1β maturation. Loss of alveolar epithelial Nlrp3 limited recruitment of pro-fibrotic Siglec-F⁺ neutrophils, which expressed elevated fibrogenic mediators, and reduced airway neutrophil elastase levels. At day 14, Nlrp3 deficiency reduced persistent Siglec-F⁺ neutrophils and broadly reduced airway inflammatory cytokines, accompanied by decreased lung damage, alveolitis, collagen deposition, fibrotic nodule expansion, and α-SMA expression, independent of detectable TGFβ changes. By day 28, during the chronic fibrotic phase, alveolar epithelial Nlrp3 deficiency continued to confer protection, reducing persistent inflammation, collagen accumulation, and fibrotic nodule size. In parallel, deletion of Nlrp3 in Scgb1a1⁺ bronchiolar epithelial cells reduced early inflammasome activation at day 3 and similarly decreased chronic lung inflammation, collagen deposition, and fibrotic nodule expansion, without affecting nodule number or cellularity at day 28.</p><p><strong>Conclusions: </strong>These findings establish epithelial Nlrp3 as a critical driver of silica-induced fibrotic remodeling through IL-18 and pro-fibrotic neutrophil recruitment, independent of canonical TGFβ mechanisms. This epithelial-centric paradigm provides a rationale for precision therapeutic strategies targeting epithelial NLRP3.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure to polylactic acid microplastics during puberty increases the risk of skeletal dysplasia by disrupting arachidonic acid metabolism in osteoblasts.","authors":"Yao Zhang, Zongheng Cai, Xinyu Luo, Hao Chen, Xing Zhang, Chun Pan","doi":"10.1186/s12989-026-00679-4","DOIUrl":"https://doi.org/10.1186/s12989-026-00679-4","url":null,"abstract":"<p><p>Biodegradable polylactic acid (PLA) plastic is considered to be an effective method to solve the global white pollution caused by petroleum-based plastics. Its wide application in disposable tableware and food packaging has led to the risk of human exposure to PLA microplastics (MPs), but its impact on bone health is unclear. Our study investigated the skeletal developmental toxicity of PLA-MPs at environmentally accessible concentrations in adolescent mice and its potential mechanism. Here we demonstrated that PLA-MPs treatment in adolescent mice showed significant skeletal developmental toxicity, manifested as shortened body length and slowed growth of femur and tibia. Further analysis found that PLA-MPs caused a diminution of epiphyseal plate thickness, a decrement in the count of bone trabeculae, damaged femoral microstructure, and inhibited femoral new bone formation. Notably, PLA-MPs enter osteoblasts and destroy their osteogenic differentiation, resulting in a dose-dependent damage that reduces the formation of calcium nodules. Transcriptome analysis further demonstrated that PLA-MPs exposure was associated with disrupted arachidonic acid metabolism, which may contribute to impaired osteoblast formation, especially Cyp2j5 gene and its downstream metabolite epoxyeicosatrienoic acids were significantly inhibited. Subsequent studies have indicated that Ophiopogonin D (Oph D) can activate Cyp2j5 signal to alleviate PLA-MPs-induced damaged osteoblast differentiation. Furthermore, alleviating impaired differentiation function of osteoblasts using Oph D can significantly improve the reduction of trabecular bone and bone microstructure damage caused by adolescent PLA-MPs exposure. This study not only identifies a potential mechanistic association between PLA-MPs exposure and poor bone development, but also emphasizes the need for targeted interventions to protect bone health in adolescent children and the broader impact on environmental and public health policies.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147778205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simulated aquatic aging exacerbates pulmonary toxicity of graphite nanoplatelets by mechanically and chemically induced surface oxidation, enhancing oxidative potential.","authors":"Karthika Viswanathan, Youn-Joo Jung, Maruthupandy Muthuchamy, Soyeon Jeon, June-Woo Park, Wan-Seob Cho","doi":"10.1186/s12989-026-00678-5","DOIUrl":"10.1186/s12989-026-00678-5","url":null,"abstract":"<p><strong>Background: </strong>Graphite nanoplatelets (GNPs) are increasingly used in advanced materials, yet their environmental transformation and resulting health impacts remain poorly understood. This study investigated how long-term aquatic aging alters the physicochemical properties and pulmonary toxicity of GNPs.</p><p><strong>Results: </strong>Pristine GNPs (PGNPs) were aged for 26 months in water containing sand under constant agitation to simulate natural mechanical and chemical weathering, yielding aged GNPs (AGNPs) with increased surface oxidation level, smaller lateral dimensions, and improved hydrophilicity. These alterations enhanced the intrinsic oxidative potential of AGNPs by 1.28-1.40-fold relative to PGNPs. Following a single intratracheal instillation in mice (25-100 µg/mouse), AGNPs induced significantly stronger pulmonary inflammation at both 24 h and 7 days, characterized by elevated neutrophil infiltration, increased levels of lactate dehydrogenase, total protein, and pro-inflammatory cytokines in bronchoalveolar lavage fluid. Although both materials showed a similar clearance pattern, AGNPs showed a slightly prolonged retention compared to PGNPs (half-life: AGNPs 10 days, PGNPs 5.5 days). Differentiated THP-1 macrophages and A549 cells exposed to AGNPs showed higher cytotoxicity, intracellular reactive oxygen species (ROS) generation, and cytokine release than PGNPs, confirming the in vivo findings. Correlation analysis revealed that ROS levels were strongly associated with inflammatory and cytotoxic endpoints (Pearson r > 0.90), indicating that oxidative stress is a key mechanism of GNP-induced toxicity.</p><p><strong>Conclusions: </strong>These findings demonstrate that simulated aquatic aging enhances the oxidative potential and pulmonary toxicity of GNPs through mechanically and chemically induced surface oxidation, highlighting the need to consider environmental transformation in nanomaterial hazard assessment and life-cycle-based safety assessment.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aged automobile cabin air filters as secondary pollution sources: mechanistic insights into NLRP3 inflammasome activation and discovery of a natural inhibitor.","authors":"Jiaqi Tian, Yi Guan, Zengfeng Li, Qiang Li, Dandan Song, Ning Li, Xiaotan Shi, Yongfei Zheng, Shuyin Duan, Lin Zhang","doi":"10.1186/s12989-026-00674-9","DOIUrl":"10.1186/s12989-026-00674-9","url":null,"abstract":"<p><p>Automobile cabin air filter-deposited particulate matter represents an underappreciated exposure source, yet the differential toxicity between filter sides and underlying mechanisms remain unclear. Here, we systematically investigated particles extracted from the inside (cabin-facing) and outside (environment-facing) membranes of used automobile air filters. Morphological analysis revealed that inside particles exhibited smaller size and greater dispersion, consistent with ultrafine particle enrichment. In a murine exposure model, inside particles induced more severe pulmonary inflammation, histopathological injury, and elevated interleukin-1β levels compared to outside particles at equivalent doses. Single-cell RNA sequencing identified alveolar macrophages as the predominant responding cell type, with significant enrichment of the NOD-like receptor signaling pathway. Mechanistic investigations demonstrated that particle exposure activated the NLRP3 inflammasome and triggered Gasdermin D-mediated pyroptosis through a reactive oxygen species-independent pathway. Furthermore, we employed structure-based virtual screening of over two thousand natural compounds, from which we identified the cyclic dipeptide Cyclo-(Tyr-Phe) as a novel NLRP3 inhibitor. Molecular dynamics simulations and cellular thermal shift assays confirmed direct NLRP3 binding, while functional validation demonstrated that Cyclo-(Tyr-Phe) effectively attenuated particle-induced pyroptosis and inflammatory responses. These findings illuminate the heightened toxicity of ultrafine-enriched filter particles and provide a promising therapeutic candidate for mitigating particle-induced lung injury.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147675762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pollutant particles enhance house dust mite induced type 2 inflammation and the recruitment of monocyte derived Cd11c⁺ Gpnmb⁺ macrophages to the airway lumen.","authors":"Kirsty Meldrum, Ayokulehin Muse Kosoko, Martin Oliver Leonard","doi":"10.1186/s12989-026-00675-8","DOIUrl":"10.1186/s12989-026-00675-8","url":null,"abstract":"<p><strong>Background: </strong>Air pollution particles exacerbate allergic asthma and can enhance inflammatory responses to allergen exposure, but the cellular mechanisms involved remain incompletely defined. We examined how diesel exhaust particles (DEP) enhance house-dust-mite (HDM) inflammatory responses within the lung and characterised potential mechanisms that may contribute to enhanced type 2 (T2) inflammatory responses.</p><p><strong>Results: </strong>In mice subjected to repeated intranasal exposures, DEP alone had modest effects, whereas DEP + HDM markedly increased type-2 inflammatory indicators (Serum IgE; Airway Il13, Il4 & Tslp) and eosinophilia alongside expansion of Th2 cells. Bulk transcriptomics showed far stronger differential expression in luminal airway cells than tissue, with a DEP + HDM-specific signature enriched for mast cells, alternatively activated macrophages (AAM), and B-cells in the lumen. Combined single-cell proteomic and transcriptomic profiling identified an expanded Cd11c⁺, SiglecF⁻, Apoe⁺, Gpnmb⁺ monocyte-derived macrophage subset (RM.Gp2), which showed increased type 2 chemokines Ccl8 and Ccl24 with DEP + HDM compared to HDM alone. Trajectory analysis placed RM.Gp2 downstream of Ccr2⁺ monocyte derived population, and protein/mRNA data supported a Ccl2-Ccr2-dependent influx that enlarges the RM.Gp2 pool. High-content imaging confirmed increased RM.Mo and RM.Gp2 numbers and higher total luminal Ccl8/Ccl24. F4/80⁺ luminal airway macrophages isolated from DEP pre-treated mice, demonstrated enhanced upregulation of Ccl8 and Ccl24 mRNA in response to ex vivo Il-4/Il-13 treatment, compared to macrophages isolated from control mice. Examination of an additional particle type (CeO₂ Nanoparticles) in the same exposure model, revealed a shared luminal transcriptomic response and AAM/chemokine programme as with DEP.</p><p><strong>Conclusions: </strong>Our data suggests that pollutant particles such as DEP may contribute to enhanced HDM induced type 2 inflammation by expanding Ccr2-dependent monocyte-derived macrophages into the airway lumen and licensing a Th2-cytokine-responsive chemokine programme (Ccl8- Ccr8 to recruit Th2 cells; Ccl24-Ccr3 to recruit eosinophils). These findings identify luminal recruited macrophages as important targets in allergic inflammation within the lung, providing insight into potential mechanisms from which exposure and disease mitigation strategies may be developed.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147662935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A simple and reliable method for the qualitative and quantitative analysis of nano- and microplastics in organs for controlled preclinical studies.","authors":"Soyeon Jeon, Gyuri Kim, Jun Hui Jeon, Sung Ik Yang, Kyuhong Lee, June-Woo Park, Wan-Seob Cho","doi":"10.1186/s12989-026-00677-6","DOIUrl":"10.1186/s12989-026-00677-6","url":null,"abstract":"<p><strong>Background: </strong>Toxicity studies of microplastics increasingly emphasize the importance of particle retention, transformation, and physicochemical properties within biological systems, as these factors critically influence hazard identification and dose-response interpretation. However, quantitative and qualitative analyses of microplastics in biological matrices remain technically challenging, and many existing digestion-based methods can alter particle properties, thereby confounding toxicological outcomes. Herein, we propose a novel methodology to provide quick, easy, non-destructive, cost-efficient, and reliable outcomes by offering a particle collection method for microplastics as-present in organs using proteinase K (PK) digestion and a simple quantification method based on ultraviolet-visible (UV-Vis) spectrophotometry.</p><p><strong>Results: </strong>The test microplastic samples comprised three spherical polystyrene (0.1, 1, and 100 μm), two fragmented polystyrene (1 and 100 μm), one spherical polyethylene (10 μm), one fragmented polyethylene (100 μm), and two fragmented polypropylene (1 and 100 μm). Particles as-present in organs were successfully collected by conducting PK tissue digestion at 5 µg PK per mg dried tissue. The collected particles were then quantified using a standard curve, with absorbance measured at 750 nm. Spiking experiments with microplastics in mouse lung and mussel tissues showed > 90% accuracy and recovery for all test particles. Because the PK-based particle collection method is non-destructive, the collected particles can be further used to evaluate their physicochemical properties, such as size, shape, composition, and oxidative potential. However, the plastics treated with both acids and alkalis exhibited significant morphological, optical, and chemical changes, indicating that these methods are destructive to particles.</p><p><strong>Conclusion: </strong>Therefore, this simple, non-destructive approach enables quantitative and qualitative analyses for laboratory toxicological studies and qualitative identification of microplastics in unknown biological samples, providing a valuable tool for future toxicity and environmental research.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13104356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal exposure to titanium dioxide nanoparticles disrupts ultrasonic vocalization development in mouse offspring.","authors":"Marie Boulain, Taner Aktas, Gilles Courtand, Grégory Barrière, Muriel Thoby-Brisson, Didier Morin, Laurent Juvin","doi":"10.1186/s12989-026-00668-7","DOIUrl":"10.1186/s12989-026-00668-7","url":null,"abstract":"<p><strong>Background: </strong>Early neurodevelopment is a critical period during which environmental exposures can have lasting effects on brain function and behavior. One key indicator of early neurodevelopmental integrity in rodents is the production of neonatal ultrasonic vocalizations (USVs), which are essential for maternal-offspring communication. Given the widespread use of titanium dioxide nanoparticles (TiO2NPs) in food and consumer products, there is growing concern that perinatal exposure to these particles may interfere with normal neurodevelopment. However, the effects of TiO2NPs exposure on USV production remain poorly investigated.</p><p><strong>Results: </strong>In the present study, pregnant mice were orally exposed to TiO2NPs (200 µg/g) from conception to weaning, and their offspring underwent a maternal separation test to assess USVs between postnatal day P2 and P13. TiO2NP-exposed pups exhibited a significant reduction in the number of USVs at P6-7, accompanied by a delayed peak vocalization period. This reduction was primarily attributable to shorter vocalization series rather than fewer isolated calls. Additionally, acoustic analysis revealed that pups emitted two types of USVs, simple and complex, both of which were significantly reduced in number at P6-7 in the exposed group. Fast Fourier transform (FFT)-based analysis showed that complex USVs had a lower mean frequency, while both call types exhibited increased variability in mean frequency. Furthermore, TiO2NP-exposed pups displayed alterations in USV syntax, including a lower proportion of simple USVs and disrupted developmental maturation of call structure. Electrophysiological recordings revealed that the intermediate reticular oscillator (iRO), a key brainstem center involved in vocalization control, exhibited reduced excitability and an increased activity variability in exposed pups, suggesting that nanoparticle exposure compromises vocal motor regulation at the neural level. Lastly, playback experiments demonstrated that USVs from TiO2NP-exposed pups failed to elicit appropriate maternal attraction, indicating impaired communicative effectiveness.</p><p><strong>Conclusions: </strong>Perinatal exposure to TiO2NPs disrupts the normal development of USVs, impairing both vocalization patterns and neural excitability of the iRO. These changes may contribute to altered maternal-offspring interactions and highlight the potential neurodevelopmental risks of early-life TiO2NPs exposure. Given the widespread presence of TiO2NPs in consumer products, further research is necessary to assess their long-term consequences on neural circuits underlying communication and social behavior.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13104461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147609587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal PM_2.5 exposure induces insulin resistance in adult male mouse offspring via gut-liver axis.","authors":"Renjie Hu, Wenbin Zhao, Wenjun Fan, Ran Li, Lu Zhang, Li Qin, Huanhuan Zhu, Xuan Zhu, Qinghua Sun, Guifen Qiang, Cuiqing Liu","doi":"10.1186/s12989-026-00676-7","DOIUrl":"10.1186/s12989-026-00676-7","url":null,"abstract":"<p><strong>Background: </strong>The rising prevalence of metabolic diseases represents a global health challenge, with metabolically unhealthy normal-weight (MUHNW) individuals remaining largely overlooked. In addition to direct fine particulate matter (PM_2.5) inhalation, there is growing recognition that maternal PM_2.5 exposure may be a contributing environmental factor for metabolic disorders. However, the mechanisms by which maternal PM_2.5 exposure induced metabolic disorders in the offspring remain unknown.</p><p><strong>Methods: </strong>Eight-week-old pregnant C57BL/6N mice were exposed to either filtered air (FA) or ambient PM_2.5 throughout gestation, from gestational day 0 to 18, using a whole-body inhalation exposure system. Eight-week-old male C57BL/6N mice were treated once daily for three consecutive days with an antibiotic cocktail containing 1 g/L ampicillin, 0.5 g/L neomycin, 0.5 g/L vancomycin, and 1 g/L metronidazole to generate pseudo-germ-free mice. Subsequently, fecal microbiota from maternal PM_2.5-exposed three-week-old male mouse offspring (donor) were transplanted to pseudo-germ-free mice (recipient) via oral gavage twice weekly for five weeks. After fecal microbiota transplantation (FMT), fecal samples from donor and recipient mice were collected for full-length 16S rRNA sequencing. Liver tissue from donor mice was analyzed by 5R 16S rRNA sequencing.</p><p><strong>Results: </strong>Maternal PM_2.5 exposure induced non-obese insulin resistance in adult male mouse offspring, with the liver identified as a susceptible organ characterized by suppressed AKT phosphorylation. Subsequently, systemic and hepatic insulin resistance were recapitulated in pseudo-germ-free mice, which received gut microbiota from maternal PM_2.5-exposed mouse offspring via FMT. Mechanistically, the increased abundance of Helicobacter hepaticus contributed to DNA damage-mediated colonic barrier injury. This impaired colonic barrier facilitated gut-to-liver translocation of bacteria and lipopolysaccharide (LPS), which triggered hepatic inflammation via activation of TLR4 signaling pathway, ultimately leading to insulin resistance.</p><p><strong>Conclusions: </strong>These findings indicated a causal role for gut microbiota dysbiosis in maternal PM_2.5 exposure-induced non-obese insulin resistance in the offspring, providing potential insights into the developmental origins of MUHNW from the perspective of maternal exposure to air pollution.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13085421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147593880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}