Biometals最新文献

{"title":"Meta-analysis reveals a core iron-responsive gene signature in Mycobacterium tuberculosis linking siderophore biosynthesis, virulence, and metabolic adaptation.","authors":"Gauri Shankar, Yusuf Akhter","doi":"10.1007/s10534-026-00818-6","DOIUrl":"https://doi.org/10.1007/s10534-026-00818-6","url":null,"abstract":"<p><p>The meta-analysis integrates transcriptomic data from two independent datasets (GSE8732 and GSE84554) to elucidate Mycobacterium tuberculosis (Mtb)'s transcriptional response to iron limitation, a key host defense mechanism. The study identifies a core set of consistently differentially expressed genes (DEGs) critical for Mtb's survival under iron-restricted conditions. Key upregulated genes include those involved in siderophore biosynthesis (mbtA, mbtB, mbtE, mbtI), which are essential for iron acquisition, and components of the ESX secretion system (esxG, esxH, esxR, esxS), linking iron scavenging to virulence. Additionally, PE/PPE family genes (PPE37, PE5), implicated in immune evasion, were consistently upregulated, suggesting their role in host-pathogen interactions during iron scarcity. Conversely, downregulated genes included iron storage proteins (bfrA), regulatory factors (ideR, sigB, rpoC), and metabolic enzymes (aspC, frdA), reflecting a strategic shift away from iron-dependent processes to conserve resources. Temporal analysis revealed a dynamic adaptation process: early-phase responses prioritized iron acquisition, while prolonged starvation induced metabolic restructuring (e.g., upregulation of fadD33, kasB) and stress responses (grpE). The iron-dependent regulator IdeR emerged as a central player, derepressing iron acquisition genes under low iron but also revealing additional regulatory layers. The consistent DEGs across datasets validate their biological significance and highlight potential therapeutic targets, such as siderophore biosynthesis and ESX systems, to disrupt Mtb's adaptation during infection. This study advances insights into Mtb's pathogenicity and survival strategies under host-imposed iron restriction, offering a framework for novel anti-tuberculosis interventions.</p>","PeriodicalId":491,"journal":{"name":"Biometals","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative proteomics insights into the response mechanisms of Aeromonas hydrophila to chromium stress.","authors":"Huaiyao Zhang, Chenghao Shen, Xin Zeng, Xiaowei Zhang, Binghui Zhang, Yuyue Xie, Xiangmin Lin, Lingli Lian","doi":"10.1007/s10534-026-00813-x","DOIUrl":"https://doi.org/10.1007/s10534-026-00813-x","url":null,"abstract":"<p><p>Aeromonas hydrophila, an opportunistic pathogen of aquatic fish, can survive under various environmental stresses, including exposure to chromium (Cr), a heavy metal that exerts dose-dependent toxic effects on bacteria. Elucidating the mechanism underlying its response to chromium stress holds considerable significance, while related studies are still scarce. In this study, growth curve experiments showed that potassium dichromate inhibited bacterial growth in a concentration-dependent manner. The concentration of 0.15 mg/mL, which induces significant but non-lethal growth inhibition, was selected to probe the proteomic response under growth-inhibitory stress. Quantitative proteomics analysis identified 678 altered proteins under chromium stress with 294 proteins increased and 384 decreased abundances. Functional enrichment analyses revealed that chromium mainly suppressed pathways like energy metabolism, amino acid metabolism, and bacterial chemotaxis, while activating defense mechanisms such as DNA repair and siderophore transport. RT-qPCR analysis confirmed the transcriptional upregulation of several siderophore transport-related genes and one DNA repair-related gene, supporting the trend observed in proteomics analysis. Further analysis showed antioxidants including epicatechin, ascorbic acid and gallic acid alleviated chromium toxicity, suggesting that reactive oxygen species (ROS) play an important role in chromium stress. Additionally, deletion of AHA_2968, encoding a GGDEF-domain protein, markedly enhanced the sensitivity of A. hydrophila to chromium, suggesting that c-di-GMP signaling may be involved in the response to chromium stress. In summary, our findings provide novel insights into the molecular responses of A. hydrophila to growth-inhibitory chromium stress.</p>","PeriodicalId":491,"journal":{"name":"Biometals","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overlaps in mammalian iron and manganese homeostasis: recent advances.","authors":"Milankumar Prajapati, Lauren Chiu, Jaydyn Akpengbe, Christos Costeas, Thomas B Bartnikas","doi":"10.1007/s10534-026-00808-8","DOIUrl":"10.1007/s10534-026-00808-8","url":null,"abstract":"<p><p>Iron and manganese are essential nutrients yet toxic in excess. Given this, levels of these metals are carefully regulated in the body by specific molecular mechanisms. In this review, we discuss recently reported overlaps in iron and manganese homeostasis in mammalian systems, with a focus on intestinal absorption and gastrointestinal excretion. We begin with the current understanding of iron and manganese homeostasis, then present causes and consequences of imbalances in levels of these metals in the body. Notably, while manganese is best known as a neurotoxicant, multiple recent studies have reported that variations in manganese levels correlate with a wide variety of parameters of health and disease. We then highlight deficiency in the manganese transport protein SLC30A10, the first reported inherited cause of manganese excess, and recent studies of SLC30A10 from our group and others that demonstrate three intriguing overlaps between iron and manganese homeostasis. First, intestinal iron transporters DMT1 and ferroportin are essential for manganese absorption and overload in SLC30A10 deficiency. Second, intestinal SLC30A10 downregulates manganese absorption when pathways of iron absorption are upregulated. Third, manganese excess promotes SLC30A10 expression by perturbing regulation of hypoxia-inducible factors, transcription factors that are essential for the cellular response to iron imbalance. We also briefly review SLC39A14 and SLC39A8 deficiency, two other inherited diseases of manganese imbalance, and the current understanding of the function of SLC39A14 and SLC39A8. We conclude with a discussion of active, unresolved questions in need of further investigation that will enhance our understanding of the interplay between iron and manganese homeostasis in mammalian systems.</p>","PeriodicalId":491,"journal":{"name":"Biometals","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13094726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147669576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vanadium salt inhibits osteoclast formation and preserves bone integrity in a rat model of type-1 diabetes associated bone loss.","authors":"Joshua Greendyk, James Thornton, Darian Napoleon, Michael Greenberg, Anthony Lin, Mike Levidy, Jonathan R Lopez, Maximilian Muñoz, Kevin Innella, Yazan Kadkoy, Maya Deza Culbertson, Jessica A Cottrell, J Patrick O'Connor, Joseph Benevenia, David N Paglia, Sheldon S Lin","doi":"10.1007/s10534-026-00810-0","DOIUrl":"https://doi.org/10.1007/s10534-026-00810-0","url":null,"abstract":"<p><p>The effects of vanadyl acetylacetonate (VAC) were evaluated on femur intramedullary osteoclasts in a rat model of type 1 diabetes (T1D) associated bone remodeling. In this study, BB Wistar rats were administered intramedullary injections consisting of either VAC at a dose of 1.5 mg/kg or a control saline solution. These injections were administered at least 12 weeks after the onset of T1D (i.e., treatment began ≥ 12 weeks after diabetes onset) to allow for the establishment of diabetic bone changes. At 4 weeks following treatment, the femurs treated with VAC exhibited a significant increase in trabecular thickness, specifically a 19.03% increase (p < 0.05). Osteoclasts, which were identified using TRAP staining, were found to be reduced in number at both 6 and 8 weeks in the femurs that received VAC treatment (p < 0.05). Likewise, when VAC was added to culture media, it resulted in a substantial decrease in osteoclast formation in vitro (8.1 ± 16.8 vs. 91.6 ± 16.0 cells, p < 0.001). In addition, expression of Dcstamp was significantly decreased in VAC-treated femurs compared to those treated with saline (p < 0.05). Taken together, this study demonstrates that intramedullary VAC delivery appears to inhibit T1D-related bone loss by impairing the process of osteoclastogenesis.</p>","PeriodicalId":491,"journal":{"name":"Biometals","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147607799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aromatic amino acid metabolism shapes autophagy-mediated adaptation to iron deprivation in glioblastoma cells.","authors":"Kai Zhao, Lena Ludwig-Radtke, Yukai Wang, Tillmann Rusch, Christopher Nimsky, R Verena Taudte, Jörg W Bartsch","doi":"10.1007/s10534-026-00809-7","DOIUrl":"https://doi.org/10.1007/s10534-026-00809-7","url":null,"abstract":"<p><p>Glioblastoma (GBM) displays profound iron dependence and metabolic plasticity, yet how iron deprivation interfaces with stress-response pathways and amino acid metabolism in GBM remains incompletely understood. Deferoxamine (DFO), an iron chelator and hypoxia mimetic, is widely used experimentally, but the integration of autophagy, apoptosis, and ferroptosis under DFO-induced stress is unclear. This study aims to clarify how iron chelation reshapes stress signaling and metabolism in GBM cells and to define the role of aromatic amino acid metabolism in autophagy-mediated adaptation to iron deprivation. U87 and U251 human GBM cell lines were treated with DFO in the presence or absence of pan-caspase inhibitor Q-VD-OPh, the autophagy inhibitor CQ, or L-phenylalanine and L-tyrosine. AlamarBlue assessed cell viability. Hypoxia, autophagy, apoptosis, and ferroptosis-related genes and proteins were analyzed by qPCR, western blotting, and immunofluorescence. Global metabolic alterations were profiled by untargeted UHPLC-HRMS-based metabolomics followed by multivariate and pathway enrichment analyses. DFO stabilized HIF-1α, robustly induced hypoxia-related gene expression, and reduced GBM cell viability, with U251 cells being more sensitive than U87. DFO induced an autophagy response associated with ULK1 upregulation and reduced mTOR transcript levels, accompanied by increased LC3-II and changes in p62 levels. A lysosomal inhibition-based assay further supported increased autophagic flux, and meanwhile engaged apoptosis, particularly in U251, where Q-VD-OPh significantly rescued viability. In contrast, DFO induces an iron-starvation signature and maintains ferroptosis-associated antioxidant markers (GPX4/SLC7A11). CQ co-treatment potentiated DFO cytotoxicity in both lines, indicating a cytoprotective role of autophagy. Metabolomics revealed extensive DFO-induced reprogramming of amino acid and central carbon metabolism, with aromatic amino acid metabolism emerging as key pathway. DFO decreased intracellular L-phenylalanine and L-tyrosine in U87 but not U251 cells. Combined L-P + L-T supplementation attenuated DFO-induced autophagic responses and further enhanced DFO-mediated cytotoxicity. Iron chelation by DFO establishes a multifaceted stress state in glioblastoma cells, characterized by hypoxia-like transcription, cytoprotective autophagy, apoptosis, and ferroptosis resistance, coupled to profound amino acid-centric metabolic remodeling. Aromatic amino acid metabolism modulates autophagic responses and a determinant of GBM susceptibility to iron deprivation. Therefore, targeting aromatic amino acid metabolism to disable protective autophagy may enhance the therapeutic efficacy of iron-based strategies in GBM.</p>","PeriodicalId":491,"journal":{"name":"Biometals","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147589261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic function of ars genes in arsenic detoxification and biosynthesis of organoarsenicals.","authors":"Jian Chen, Thiruselvam Viswanathan, Barry P Rosen","doi":"10.1007/s10534-026-00807-9","DOIUrl":"https://doi.org/10.1007/s10534-026-00807-9","url":null,"abstract":"<p><p>Arsenic contamination poses a major threat to ecosystems and human health. Microorganisms have developed diverse resistance mechanisms to manage arsenic toxicity, primarily through the function of arsenic resistance (ars) operons. These gene clusters, often located close together in the genome, operate synergistically to regulate and enhance arsenic resistance. The ars genes encode proteins involved in arsenic transcriptional regulation, transport, reduction, and methylation, leading to arsenic detoxification and also the formation of complex compounds such as arsenosugars and arsinothricin ((2-amino-4-(hydroxymethylarsinoyl)butanoate, AST). Cooperative ars gene interactions have been involved in coordinated expression and regulation, working together to improve the organism's capacity to decrease arsenic toxicity, resulting in more effective detoxification processes. Within ars operons, in addition to individual single-function genes, there are also fusion genes, which are genetic sequences formed from the merging of two distinct ars genes. These fusions provide microorganisms with novel capabilities that enhance their adaptability and survival under arsenic exposure. This review explores the diversity and organization of ars operons across microbial species, emphasizing the cooperative interactions between ars genes, including fusion genes, and their role in the synthesis of complex arsenic compounds. These processes illustrate the evolutionary adaptation and ecological significance of the mechanisms of arsenic biotransformations. Understanding these synergistic interactions not only highlights microbial survival strategies but also offers insights into potential applications for arsenic-based antibiotics development and environmental management.</p>","PeriodicalId":491,"journal":{"name":"Biometals","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147497249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dioxazolium desferrioxamine as a cell permeant chelator of intracellular labile iron.","authors":"Pradnya K Pachpatil, Seema V Kanojia, Binita K Kumar, Dibakar Goswami","doi":"10.1007/s10534-026-00805-x","DOIUrl":"https://doi.org/10.1007/s10534-026-00805-x","url":null,"abstract":"<p><p>Desferrioxamine (DFO), a clinically used chelator for iron overload, has poor cell permeability, leading to its limited ability to chelate intracellular labile iron pool (LIP). Herein, a dioxazole masking group has been introduced for one of the hydroxamate groups of DFO in an endeavor to decrease its hydrophilicity. The masking group got deprotected selectively in presence of labile iron, thereby regenerating the hexadentate complex DFO-Fe, eliminating the chances of forming toxic partially chelated complexes. The iron binding abilities and the antioxidant properties of the DFO-derivative were found to be similar to DFO. The ability to chelate intracellular LIP in iron-overloaded cells was found to be higher in the Dioxazolium-DFO compared to DFO. This opens up a new avenue in using dioxazolium masking group for hydrophilic cell-impermeable drugs belonging to hydroxamate group.</p>","PeriodicalId":491,"journal":{"name":"Biometals","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147472075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of biogas slurry abate Pb metal uptake and oxidative stress in maize (Zea mays L.) by modulating seedling emergence, antioxidant defense, and root structural-functional traits.","authors":"Hafeez Ur Rehman, Athar Mahmood, Muhammad Shahbaz, Zubair Aslam","doi":"10.1007/s10534-026-00806-w","DOIUrl":"https://doi.org/10.1007/s10534-026-00806-w","url":null,"abstract":"<p><p>Lead (Pb) contamination in soil significantly reduces crop productivity, presents considerable environmental and health hazards, and requires the development of effective remediation strategies. The use of biogas slurry derived from agricultural crop residues offers a promising approach to reduce Pb bioavailability in soil and alleviate its toxicity in maize seedlings, a topic that has not been extensively documented. Incorporating biogas slurry into soil immobilises Pb via adsorption. The biogas slurry reduced Pb uptake to plant aerial parts and ameliorated the emergence of maize seedlings by increasing germination rate. Consequently, Pb concentration in maize roots, shoots, and grains decreased by 68.17%, 55.17% and 62.10%, respectively. Furthermore, biogas slurry amendment markedly enhanced plant growth, stimulated antioxidant activity, and upregulated key non-enzymatic antioxidants, i.e., TPC, TFC, and DPPH. Moreover, organic addition ameliorated root architectural and functional traits like increased RL (99.01%), RPA (258.46%), and RSA (284.75%) more compared to the control. Conversely, it reduced BAC (15.57%) and BCF (35.75%). Analysis of organic osmolytes (TSP increased by 45.11%; TSS up to 51.04%) also elucidated that biogas slurry contribute to improved stress tolerance under Pb toxicity. These results offer new perspectives for sustainable agriculture by demonstrating that biogas slurry can decrease Pb mobility in the soil-plant system, thereby providing a potential solution to the ongoing issue of heavy metal contamination in agricultural soils.</p>","PeriodicalId":491,"journal":{"name":"Biometals","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147472125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mycosorption of copper by Aspergillus terreus SJP02: process optimization and underlying mechanism.","authors":"Shobham, Mamta, Sanjay Kumar Verma, Suresh Gupta, Jitendra Panwar","doi":"10.1007/s10534-026-00804-y","DOIUrl":"https://doi.org/10.1007/s10534-026-00804-y","url":null,"abstract":"<p><p>Copper, a naturally occurring element in the Earth's crust and an essential micronutrient, is widely used in various industries. However, excessive exposure of Cu²⁺ions often resulting from contaminated drinking water, food and personal health care products can harm human health by impacting the liver, heart, digestive and nervous system. The present study revealed high Cu²⁺ removal potential of Aspergillus terreus SJP02 isolated from metal contaminated industrial sites. The mycosorbent demonstrated maximum sorption capacity of 11.45 ± 0.2 mg g^-1 in 120 min. Acid digestion studies suggested adsorption as primary mechanism (86.79%) for removal of Cu²⁺. FE-SEM-EDX analysis confirmed deposition of Cu²⁺ on fungal biomass. FTIR analysis showed presence of various functional groups of proteins and polysaccharides which would have been involved in the adsorption Cu²⁺. Various adsorption isotherms were used to analyze type and bonding between adsorbate and mycosorbent. Pseudo- first and second order were applied to understand the correlation in time course data, rate constant, and kinetic parameters. Langmuir isotherm showed maximum Cu²⁺ sorption capacity of 11.35 mg g^-1. The experimental results correlated with the tested isotherm and kinetic models. The simultaneous removal of Cu²⁺and Zn²⁺ ions revealed preferential uptake of Cu²⁺ over Zn²⁺ ions by the mycosorbent. Notably, present study demonstrated better sorption capacity in significantly shorter equilibration time in comparison to previous reports and suggests that A. terreus SJP02 holds strong potential for future industrial-scale mycoremediation of Cu²⁺ contaminated wastewater.</p>","PeriodicalId":491,"journal":{"name":"Biometals","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147429572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-exposure to arsenic and nickel induces oxidative stress and mineral imbalance, impairing male reproductive parameters in Wistar rats.","authors":"Thainá Iasbik-Lima, Luiz Otávio Guimarães-Ervilha, Tayná Bolsam da Silva, Renê Chagas da Silva, Mariana Machado-Neves","doi":"10.1007/s10534-026-00797-8","DOIUrl":"https://doi.org/10.1007/s10534-026-00797-8","url":null,"abstract":"<p><p>Simultaneous exposure to multiple toxic metals is a common scenario in environmental contamination. Among these metals, arsenic and nickel are widely distributed pollutants with well-established toxic effects. However, their combined impact on male reproductive physiology and micromineral homeostasis remains poorly understood. This study evaluated the effects of subchronic co-exposure to arsenic (1 mg L^-1) and nickel (7 mg L^-1) in drinking water for 70 days on the hypothalamus, testis, and epididymis of adult Wistar rats. Exposed rats showed arsenic and nickel retention in all analyzed tissues, low serum testosterone levels, and alterations in the proportion of chemical elements, including copper, zinc, calcium, iron, and manganese. These findings were associated with an antioxidant enzyme dysregulation and high generation of protein carbonyls and nitric oxide in testicular and epididymal tissues, respectively. Consequently, the testes of co-exposed rats exhibited alterations in stereological and morphometric parameters, low daily sperm production, and initial histological changes in response to the toxic metals' presence. The hypothalamus exhibited focal areas of neuronal degeneration, especially in co-exposed rats. The epididymis of co-exposed animals presented focal areas of inflammatory infiltrates and germ cells within the luminal duct, with an acceleration of sperm transit time. Spermatozoa from all exposed rats showed low motility and high morphological abnormalities in the head, while the co-exposure increased the occurrence of midpiece and tail defects. These findings highlight the synergistic toxicity of arsenic and nickel on the male reproductive system after subchronic exposure, with a direct role of bioaccumulation and trace element dysregulation.</p>","PeriodicalId":491,"journal":{"name":"Biometals","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147353203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}