Environmental Toxicology最新文献

{"title":"Environmentally Relevant Concentrations of Commercial Titanium Dioxide Nanoparticles Induce Ferroptosis in HUVECs.","authors":"Fangfang Huang, Yashi Feng, Zi-An Wang, Yunchang Cao, Qiong Yan, Wuxiang Wang, Shaolong Feng","doi":"10.1002/tox.24517","DOIUrl":"10.1002/tox.24517","url":null,"abstract":"<p><p>Titanium dioxide nanoparticles (TiO₂-NPs) have been ever increasingly exposed to people through all possible routes, while studies focusing on their potential cardiovascular risks are relatively lacking, especially the underlying biological mechanisms that are not yet elucidated. In this study, the ferroptotic effect of TiO₂-NPs (30 nm) at environmentally relevant concentrations (0, 3, 12, and 48 μg/mL) on human umbilical vein endothelial cells (HUVECs) and the potential molecular mechanism were studied with the corresponding biochemical and molecular biology assays. The results showed that TiO₂-NPs at the tested concentrations could reduce HUVEC viability, but ferrostatin-1 might rescue this reduction in cell viability. Also, TiO₂-NPs exposure increased Fe²⁺, reactive oxygen species, and malondialdehyde, but decreased glutathione, mitochondrial membrane potential, and activities of anti-oxidative enzymes (catalase, superoxide dismutase, and glutathione peroxidase) in HUVECs through an integrated signaling pathway. Meanwhile, enhanced p38 protein phosphorylation and keap1 protein and decreased Nrf2 protein phosphorylation with reductions in mRNA expressions of downstream anti-oxidative enzyme genes (catalase, superoxide dismutase, glutathione peroxidase, and phospholipid hydroperoxidase) were identified in the TiO₂-NPs-exposed HUVECs. These indicated that TiO₂-NPs exposure induced ferroptosis in HUVECs via the p38/keap1 inhibiting Nrf2 pathway. EC ferroptosis will be a promising biomarker for assessing the cardiovascular health risks of environmental contaminants.</p>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":" ","pages":"1173-1183"},"PeriodicalIF":3.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763225","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":"Chlorpyrifos Induces Apoptosis in Macrophages by Activating Both Intrinsic and Extrinsic Apoptotic Pathways.","authors":"Chen-Yu Chiang, Shin-Wu Liu, Chun-Jung Chen, Wen-Ying Chen","doi":"10.1002/tox.24515","DOIUrl":"10.1002/tox.24515","url":null,"abstract":"<p><p>Although chlorpyrifos poses considerable risks to the environment and human health, it is still used in many countries. This pesticide has various toxic effects on humans, including neurotoxicity, reproductive toxicity, genotoxicity, and organ damage caused by oxidative stress and DNA damage. However, its specific toxicity to the immune system remains unclear. In this study, we explored the intrinsic and extrinsic apoptotic pathways through which chlorpyrifos induces apoptosis in macrophages. RAW 264.7 macrophages were treated with chlorpyrifos at concentrations of 0, 2, 4, 10, and 20 ppm for 3 h. Cytotoxicity was assessed using a lactate dehydrogenase assay, whereas apoptosis was evaluated through flow cytometry. The levels of cysteinyl aspartate-specific proteinase (caspase)-3, caspase-8, and caspase-9 were measured. The disruption of mitochondrial function and the expression of the death receptors Fas receptor and tumor necrosis factor-alpha receptor were assessed through JC-1 stain reagent. The release of mitochondrial cytochrome c, expression of Bcl2 family proteins, and level of cleaved caspases were analyzed through Western blotting. Chlorpyrifos induced cytotoxicity and apoptosis in a concentration-dependent manner. It activated caspase-3, caspase-8, and caspase-9, as well as disrupted mitochondrial function and Bcl2 family protein balance. Furthermore, chlorpyrifos induced the release of cytochrome c from the mitochondria and upregulated the expression of Fas receptor and tumor necrosis factor-alpha receptor. These findings suggest that chlorpyrifos induces cytotoxicity through caspase-3-dependent apoptosis via the intrinsic pathway (caspase-8 activation, mitochondrial dysfunction, Bcl2 protein imbalance, and cytochrome c release) and the extrinsic pathway (caspase-9 activation and death receptor expression).</p>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":" ","pages":"1150-1159"},"PeriodicalIF":3.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656479","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":"Protective Effects of Liriodendrin Against Oxidative Stress and Ferroptosis in a Mouse Model of Lipopolysaccharide‐Induced Acute Respiratory Distress Syndrome","authors":"Frank Cheau‐Feng Lin, Sheng‐Wen Wu, Shih‐Pin Chen, Chun‐Hung Su, Stella Chin‐Shaw Tsai, Yu‐Hsiang Kuan","doi":"10.1002/tox.24565","DOIUrl":"https://doi.org/10.1002/tox.24565","url":null,"abstract":"Liriodendrin, a bioactive lignan diglucoside derived from several medicinal plants, has been demonstrated to exhibit pharmacological activities, such as antioxidative and anti‐inflammatory activities. Up to now, no evidence has shown that acute respiratory distress syndrome (ARDS) is improved by liriodendrin. This study was conducted to investigate the protective effects of liriodendrin against oxidative stress and ferroptosis, key mechanisms underlying the pathogenesis of ARDS, in a mouse model of lipopolysaccharide (LPS)‐induced ARDS. To investigate the potential of liriodendrin to mitigate oxidative stress and inhibit ferroptosis, adult BALB/c male mice with LPS‐induced ARDS were treated with varying concentrations of liriodendrin. Mice received liriodendrin or dexamethasone before LPS administration. The effects of liriodendrin were evaluated by measuring changes in pulmonary histopathology, levels of lipid peroxidation, activities of antioxidative enzymes (superoxide dismutase, catalase, glutathione peroxidase), and expression of ferroptosis‐related proteins (heme oxygenase‐1, cystine/glutamate antiporter SLC7A11, glutathione peroxidase‐4). In addition, we measured the phosphorylation of nuclear factor erythroid 2‐related factor 2 (Nrf‐2), a critical regulator of cellular defense mechanisms against oxidative damage. The results indicated that liriodendrin substantially suppressed histopathological damage, reduced lipid peroxidation, and restored antioxidative enzyme activity in a dose‐dependent manner. Furthermore, this compound markedly upregulated the expression of ferroptosis‐related proteins and promoted the phosphorylation of Nrf‐2. Our findings suggest that liriodendrin protects against LPS‐induced ARDS by regulating oxidative stress and ferroptosis. The ability of liriodendrin to modulate both antioxidative responses and ferroptosis markers through Nrf‐2 phosphorylation highlights its potential as a therapeutic agent in the treatment of ARDS.","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"23 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144906455","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":"A Multibiomarker Approach to Delineate the Toxicity of Methoxyfenozide on Oncorhynchus mykiss","authors":"Tarek Fakhereddin, Demet Dogan","doi":"10.1002/tox.24562","DOIUrl":"https://doi.org/10.1002/tox.24562","url":null,"abstract":"Methoxyfenozide is a diacylhydrazine‐class insect growth regulator functioning as an ecdysone receptor agonist and inducing premature and lethal molt in susceptible larvae. This investigation was conducted to evaluate the impact of methoxyfenozide‐based commercial insecticide BYPASS on multiple end points in tissues of juvenile <jats:styled-content style=\"fixed-case\"><jats:italic>Oncorhynchus mykiss</jats:italic></jats:styled-content> following 7, 14, and 21 days of exposure to sublethal concentrations of 0.042, 0.21, and 0.42 mg/L. There was not any significant change in CF and/or HSI. The treatment resulted in diminished AChE activity in brain and muscle together with a significant decline in Na<jats:sup>+</jats:sup>, K<jats:sup>+</jats:sup>‐ATPase in gill and kidney tissues. The increase in the activities of antioxidant enzymes was followed by elevated levels of TBARS and PC throughout the experiment in all tissues, proving the status of oxidative stress. It is supported by the observed increase in 8‐OHdG level following 21 days of exposure. Caspase‐3 activity rose in a tissue‐specific manner indicating the initiation of apoptosis via the mitochondrial pathway. Multi‐biomarker responses showed concentration‐dependent effects in calculated indexes as well as higher biomarker scores for antioxidant enzymes. Overall, the neurotoxic potential and pro‐oxidant activity of BYPASS, along with its potency to cause DNA damage, apoptosis, and to disrupt osmoregulation, were revealed. The outcomes manifest the first experimental sublethal effects caused by methoxyfenozide in tissues of <jats:styled-content style=\"fixed-case\"><jats:italic>O. mykiss</jats:italic></jats:styled-content>, increasing our understanding of the risk insecticides represent and the need for strict regulatory scrutiny to mitigate the risk for non‐target organisms.","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"6 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144898075","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":"Intravenous Administration of Liposomes Encapsulating Oleanolic Acid Ameliorates Lung Injury Caused by Air Pollutants","authors":"Rioko Funayama, Aeri Toratani, Yui Uehara, Reno Kinoshita, Moeka Shimada, Rion Imai, Mikako Shimoda, Masahiro Kawahara, Susumu Hama, Ken‐ichiro Tanaka","doi":"10.1002/tox.24564","DOIUrl":"https://doi.org/10.1002/tox.24564","url":null,"abstract":"Health problems caused by air pollutants, such as fine particulate matter, are becoming more prevalent worldwide, and there is an urgent need to develop prevention and treatment strategies to combat this increase. A main mechanism by which air pollutants cause health problems is by entering the respiratory system and increasing oxidative stress. Oleanolic acid (OA) is a natural pentacyclic triterpenoid compound found in various plants that exhibits many physiological effects, including antioxidant, anticancer, and anti‐inflammatory effects. However, the effect of OA on lung injury caused by air pollutants has not been reported. We therefore analyzed the effect of OA using a mouse model of particulate matter (PM)‐induced lung injury. Oral administration of OA (5–80 mg/kg) to male ICR mice suppressed PM‐induced increases in inflammatory cell counts, protein levels, and dsDNA levels in bronchoalveolar lavage fluid; however, the effects were not significant. We therefore analyzed the efficacy of intravenous administration using OA encapsulated in polyethylene glycol‐modified liposomes (OA‐Lipo). Intravenous administration of OA‐Lipo (20–100 μg/kg) was more effective against PM‐induced lung injury at lower doses than oral administration. OA‐Lipo also significantly suppressed increased expression of inflammatory cytokines and chemokines and ROS production in PM‐exposed mice. Furthermore, intravenous administration of OA‐Lipo increased the expression of various antioxidant factors in the lungs of mice. Based on these results, we believe that OA‐Lipo exerts an antioxidant effect by increasing the expression of various antioxidant factors, thereby preventing the development of lung injury caused by air pollutants.","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"24 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144897868","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":"Toxicity Assessment of Environmental Concentrations of Ciprofloxacin in the Gills and Kidney of a Neotropical Catfish.","authors":"Lucicleide Ângelo Silva Jungles de Carvalho, Maiara Vicentini, Laís Fernanda Oya-Silva, Maritana Mela Prodocimo, Julio Cesar Moreira Brito, Tarcio Teodoro Braga, Marta Margarete Cestari, Helena Cristina Silva de Assis","doi":"10.1002/tox.24560","DOIUrl":"10.1002/tox.24560","url":null,"abstract":"<p><p>Antibiotics are frequently detected in aquatic environments, yet their effects on aquatic biota remain poorly understood. This study evaluated the toxic effects of long-term (28 days) exposure of Rhamdia quelen to environmentally relevant concentrations of ciprofloxacin (1, 10, and 100 μg L^-1), focusing on the gills and posterior kidney. After the exposure period, the fish were anesthetized and euthanized. Gills were collected for biochemical and histopathological biomarker analysis. The posterior kidney was sampled for biochemical, genotoxic, and histopathological biomarkers, as well as for the evaluation of apoptosis, cell necrosis, and the incidence of melanomacrophage centers (MMC). Results showed oxidative stress in the gills of both male and female fish. Exposure to 10 and 100 μg L^-1 CIP induced epithelial alterations in the gills in a concentration-dependent manner in both sexes. In the kidney, CIP exposure caused DNA damage and necrosis in females. At 10 μg L^-1, CIP disrupted the normal histoarchitecture of the renal parenchyma, and at 100 μg L^-1, necrosis was observed in both sexes. Exposure to 10 and 100 μg L^-1 also led to an increase in MMC. These findings indicate that contamination of aquatic habitats with antibiotics such as CIP is an environmental concern. In addition to affecting target organisms, such contaminants may have sublethal effects on fish that could extend to higher ecological levels.</p>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882476","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":"Toxicity of Commonly Used Plasticizers to the Freshwater Organisms Tilapia sparrmanii (Fish) and Caridina nilotica (Shrimp): Lethal and Sublethal Effects.","authors":"Paul Kojo Mensah, Neil John Griffin, Ntombekhaya Mgaba, Margaret Fafa Awushie Akwetey, Oghenekaro Nelson Odume","doi":"10.1002/tox.24563","DOIUrl":"10.1002/tox.24563","url":null,"abstract":"<p><p>The toxicity of microplastics in aquatic environments is usually due to plasticizers, the chemical additives that keep the plastic polymers together. Thus, the current study reports on the toxicity of three common plasticizers found in freshwater ecosystems and their impacts on two South African freshwater organisms at the organismal and biochemical levels. Tilapia sparrmanii (fish) and Caridina nilotica (shrimp) were exposed to varying concentrations of the test plasticizers, including bisphenol-A (BPA), calcium stearate (CAS), and dibutyl phthalate (DBP). The impacts of these plasticizers on mortality and biomarkers (acetylcholinesterase activity and lipid peroxidation) were investigated using 96-h short-term static nonrenewal and 21-day long-term static renewal exposure methods, respectively. All experiments were conducted in temperature-controlled rooms. Mortality was determined after 96 h, while biochemical effects were measured after 21 days. The results revealed that all three plasticizers significantly affected the mortality of both organisms. Also, acetylcholinesterase activity per unit protein in shrimp decreased significantly at all levels of exposure, while lipid peroxidation increased significantly at all levels of exposure. This study has shown that short-term and long-term exposures to the tested plasticizers could adversely impact populations of the tested organisms at both the organismal and biochemical levels.</p>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882477","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":"Integrated Use of Oxidative Stress and Histological Biomarkers of T. tinca as Indicators of 17-Alpha-Ethynylestradiol Exposure.","authors":"Ana L Oropesa,Alfonso Ramos,Cesar Fallola,Luis J Gomez","doi":"10.1002/tox.24557","DOIUrl":"https://doi.org/10.1002/tox.24557","url":null,"abstract":"The potential adverse effects of 17-alpha-ethynylestradiol (50, 100, and 500 μg EE2/kg b.w., for 30 days) on tench (Tinca tinca) were evaluated by integrating biomarkers including physiological (hepato-somatic index, spleen-somatic index, and hematocrit), oxidative stress (catalase, glutathione peroxidase, and glutathione reductase activities; total glutathione level, and lipid peroxidation), metabolic (glutathione S-transferase activity), as well as histopathological (descriptive and analytical studies) responses. The general health status of the EE2-exposed tench was disturbed based on the increase of somatic indices at high tested doses, and the development of anemia in all exposed individuals. Effective control of reactive oxygen species by the antioxidant defense system of the tench exposed to EE2 should have occurred because the lipid peroxidation process was irrelevant. Histopathological study revealed the presence of regressive changes in the liver (vacuolar degeneration, and deposits of eosinophilic material), regressive (deposits of eosinophilic material), and progressive (hyperplasia of reticuloendothelial cells) changes in the spleens of exposed fish. The severity of some lesions was dose dependent. The identified injuries did not compromise the functions of these organs. Finally, a common pattern of correlation between parameters of oxidative stress and morphological changes was not detected in the current study.","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"9 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857671","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":"Sublethal Exposure to a Chlorpyrifos-Cypermethrin Mixture Disrupts Limb Development and Causes Severe Skeletal Abnormalities in Domestic Chick Embryos.","authors":"Shashikant Sharma,Juhi Vaishnav,Pooja Raval,Suresh Balakrishnan","doi":"10.1002/tox.24558","DOIUrl":"https://doi.org/10.1002/tox.24558","url":null,"abstract":"This study examines the teratogenic effects of a sublethal dose (0.1 ppm) of a combination insecticide containing 50% chlorpyrifos (CP) and 5% cypermethrin (CM) on chick embryo limb development, revealing severe skeletal abnormalities and disruptions in key molecular pathways. Early-stage defects, including reduced somite numbers and abnormal somite patterning, were observed by day 2, with prominent limb deformities, such as limb shortening and twisted digits, emerging by days 10 and 21. X-ray analysis confirmed skeletal anomalies, while Alcian blue-Alizarin red staining revealed malformed cartilage and bone structures. Gene and protein expression analyses showed significant downregulation of Sonic hedgehog (SHH), Fibroblast Growth Factors (FGF10, FGF8), and WNT7A, leading to impaired digit formation and limb elongation. HOX genes (HOXA11, HOXD11) were initially upregulated but later downregulated, disrupting limb segment identity. Additionally, downregulation of Tbx4 and Pitx1 contributed to hindlimb malformations. Dysregulation of CASPASE3 impaired apoptosis, resulting in defective digit separation. Molecular docking studies indicated strong binding affinities of CP and CM to SHH, FGF10, WNT7A, and HOX proteins, suggesting interference with these signaling pathways. Notably, the disruption of the SHH-FGF-WNT axis, essential for limb patterning, was a key driver of these defects. Biochemical assays further revealed reduced hydroxyproline content, indicating impaired collagen synthesis. These findings highlight severe disruptions in SHH, FGF, WNT, HOX, Tbx4, and Pitx1 pathways, emphasizing the need for stricter pesticide regulations to prevent congenital limb malformations.","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"32 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144778173","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":"Cadmium-Induced Mitochondrial and MAMs Dysregulation in Rat Testis: The Protective Role of D-Aspartate.","authors":"Debora Latino,Sara Falvo,Massimo Venditti,Alessandra Santillo,Giulia Grillo,Gabriella Chieffi Baccari,Imed Messaoudi,Maria Maddalena Di Fiore","doi":"10.1002/tox.24559","DOIUrl":"https://doi.org/10.1002/tox.24559","url":null,"abstract":"Cadmium (Cd), a heavy metal, disrupts the structure of seminiferous tubules and induces cell death at multiple stages of sperm development. Cd also impairs Leydig cells (LCs), resulting in reduced serum testosterone (T) levels. This study primarily examined the impact of Cd on the mitochondrial compartment and mitochondrial-associated endoplasmic reticulum membranes (MAMs) in rat testis. Additionally, the potential of D-aspartate (D-Asp) to mitigate Cd-induced effects on steroidogenesis and spermatogenesis was assessed by administering D-Asp simultaneously or preventively with Cd. The findings demonstrated that Cd exerts reprotoxicity by affecting the mitochondrial compartment and MAMs, evidenced by an imbalance in mitochondrial dynamics, impaired mitophagy pathway, and downregulated mitochondrial biogenesis. Cd exposure also reduced lipid transfer-related factor expression and increased ER stress. Moreover, elevated levels of Ca2+ transfer-related proteins, indicative of perturbed Ca2+ homeostasis, may be associated with enhanced oxidative stress and apoptosis, which are known effects of Cd. Immunofluorescent analysis revealed that the Cd-induced mitochondrial and MAMs damage was prominent in LCs, spermatocytes, and spermatids, confirming the metal's adverse effects on steroidogenesis and spermatogenesis. Conversely, co-administration or preventive administration of D-Asp with Cd preserved mitochondrial homeostasis and functional ER-mitochondria interactions. In conclusion, the study offers novel insights into the cellular mechanisms underlying Cd-induced reprotoxicity. Importantly, it highlights the efficacy of D-Asp in preventing or counteracting testicular damage caused by Cd by enhancing mitochondrial and MAMs functionality.","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"724 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769795","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}