Ecotoxicology and Environmental Safety最新文献

{"title":"Pubertal low dose exposure to benzophenone-3 (BP-3) alters murine mammary stem cell functions","authors":"Hui Gao ,&nbsp;Xintong Yang ,&nbsp;Pengge Pan ,&nbsp;Xueli Liu ,&nbsp;Yan Ma ,&nbsp;Yadan Chen ,&nbsp;Yunxin Liu ,&nbsp;Yaqi Sun ,&nbsp;Sinan Cao ,&nbsp;Yuan Tian ,&nbsp;Yanzhou Yang","doi":"10.1016/j.ecoenv.2025.117982","DOIUrl":"10.1016/j.ecoenv.2025.117982","url":null,"abstract":"<div><div>Benzophenone-3 (BP-3) is an organic UV filter that is widely used in personal care products and has been indicated to have negative impacts on the environment and human health. The mammary glands of humans and rodents have been confirmed to be target organs affected by BP-3 exposure. However, limited information is available on the underlying mechanism currently. In this study, we hypothesized that low-concentration BP3 exposure during puberty might lead to a susceptibility to tumors through the mediation of mammary stem cells. Our findings revealed that BP-3 exposure at 50 mg/kg/day for 5 weeks during puberty led to reproductive outcomes such as reduced body weight, decreased serum estradiol and progesterone levels, and increased terminal end bud (TEB) numbers and areas. These effects were accompanied by a decreased fraction of basal mammary stem cells and decreased self-renewal and differentiation abilities of basal mammary stem cells <em>in vitro</em> and <em>in vivo</em> such as decreased sphere formation ability, a smaller 3D structure, increased branching points and hyperplastic lesions in regenerated mammary glands. Notably, for the regenerated mammary glands formed by the basal mammary stem cells of BP-3-treated mice, a decrease in the fraction of basal mammary stem cells and decreased expression levels of the milk protein β-casein and STAT5 were observed. Taken together, our data suggest that pubertal BP-3 exposure decreases the function of basal mammary stem cells such that they induce the abnormal development of mammary glands.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"292 ","pages":"Article 117982"},"PeriodicalIF":6.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143508913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Air pollution and prostate cancer: Unraveling the connection through network toxicology and machine learning","authors":"Yuqi Li ,&nbsp;Tao Zhou ,&nbsp;Zhiyu Liu ,&nbsp;Xinyao Zhu ,&nbsp;Qilong Wu ,&nbsp;Chunyang Meng ,&nbsp;Qingfu Deng","doi":"10.1016/j.ecoenv.2025.117966","DOIUrl":"10.1016/j.ecoenv.2025.117966","url":null,"abstract":"<div><h3>Background</h3><div>In recent years, air pollution has been demonstrated to be associated with the occurrence of various diseases. This study aims to explore the potential association between air pollutants and prostate cancer (PCa) and to identify key genes that may play a critical bridging role in this process.</div></div><div><h3>Methods</h3><div>This study utilized multiple online databases to obtain relevant target genes associated with air pollutants and PCa. Protein-protein interaction (PPI) analysis and visualization were conducted for the intersecting genes, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses to explore potential mechanisms. Subsequently, the best predictive model was selected through a combination of 108 machine learning algorithms. A prognostic model was constructed using the Random Survival Forest (RSF) model in conjunction with Lasso regression model, and its performance was validated in four external datasets. Finally, molecular docking analysis was conducted to investigate the interaction between key genes and air pollutants.</div></div><div><h3>Results</h3><div>Seven common air pollutants (benzene, SO₂, NO, CO, NO₂, toluene, and O₃) were selected for analysis, and 48 intersecting targets related to PCa were identified. GO and KEGG functional enrichment analyses revealed that these targets are primarily involved in regulating biological processes such as apoptosis, carcinogenesis, and cell proliferation. Based on machine learning algorithm selection, the combination of RSF and Lasso regression was identified as the optimal predictive model, which highlighted five key genes associated with air pollutants and PCa. The model exhibited strong predictive performance across all four independent external datasets. Additionally, molecular docking analysis further confirmed the potential interactions between air pollutants and these core targets.</div></div><div><h3>Conclusion</h3><div>The findings suggest that HDAC6, CDK1, DNMT1, NOS3, and DPP4 play crucial roles in the process by which air pollutants influence PCa. The results offer new insights into the molecular mechanisms linking air pollutants and PCa, highlighting the need for greater public awareness of air pollution issues.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"292 ","pages":"Article 117966"},"PeriodicalIF":6.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the viral enrichment methods and their roles in indicating wastewater-associated pollution in aquatic environments","authors":"Chen Liang ,&nbsp;Jiaxu Wang ,&nbsp;Ying Zhang ,&nbsp;Zhibo Liu ,&nbsp;Qiyu Zhu ,&nbsp;Yang Huo ,&nbsp;Zhiruo Zhang ,&nbsp;Mingxin Huo","doi":"10.1016/j.ecoenv.2025.117951","DOIUrl":"10.1016/j.ecoenv.2025.117951","url":null,"abstract":"<div><div>With the increasing need for monitoring viral contamination in aquatic environments, research has increasingly focused on utilizing viruses as indicators for microbial contamination assessment. However, studies on enrichment techniques for waterborne viruses and their occurrence and risk characteristics in the environment remain relatively limited. In this study, samples were collected over one year from a wastewater treatment plant and its receiving stream to evaluate the optimal enrichment method and to assess the presence of four representative viral indicators—human adenovirus (HAdV), crAssPhage, enterovirus (EV), and the pepper mild mottle virus (PMMoV)—in the urban water environment. The results showed that skimmed milk flocculation (SMF) and silica attachment method (SAM) achieved better viral enrichment performance in both wastewater and surface water, demonstrating greater seasonal consistency compared to other methods. Seasonal variations in virus concentrations were observed, with HAdV and crAssphage peaking in winter, while EV and PMMoV peaked in summer. Virus concentrations in wastewater treatment plants were reduced by 8.61 log10 copies/L from influent to effluent. However, residual viruses discharged into receiving streams still pose a significant environmental exposure risk, as indicated by Quantitative Microbial Risk Assessment (QMRA) results, which exhibited a strong correlation with population density. This study highlights the importance of waterborne viral indicators in developing effective water quality management strategies to ensure the safe control of viruses in aquatic environments.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"292 ","pages":"Article 117951"},"PeriodicalIF":6.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of multiple plasma metals with the risk of type 2 diabetes in Chinese adults: A cross-sectional study","authors":"Liting Yang ,&nbsp;Jin Chen ,&nbsp;Zijun Yao ,&nbsp;Junwei Cai ,&nbsp;Han Zhang ,&nbsp;Zhen Wang ,&nbsp;Huailan Guo ,&nbsp;Yongjiu Zha","doi":"10.1016/j.ecoenv.2025.117941","DOIUrl":"10.1016/j.ecoenv.2025.117941","url":null,"abstract":"<div><div>Evidence regarding the associations between co-exposure to multiple metals and diabetes risk was scarce. This study aimed to evaluate the associations of multiple metals with diabetes risk using multiple statistical methods. This cross-sectional study included 192 diabetic patients and 189 healthy subjects. We employed inductively coupled plasma mass spectrometry (ICP-MS) to determine the plasma concentrations of 18 metals. Least absolute shrinkage and selection operator (LASSO) regression, logistic regression, and Bayesian kernel machine regression (BKMR) were applied to evaluate associations of multiple metals with diabetes risk comprehensively. These models consistently suggested that aluminium and selenium were positively associated with diabetes risk, while manganese, rubidium, and lead were negatively associated with diabetes risk. Age-specific differences of selenium and sex-specific differences of manganese in diabetes risk were also observed based on stratified analyses. According to RCS analyses, we obtained dose-response relationships between metals and diabetes risk:(1) there were inverted U-shaped associations of plasma aluminium and selenium with diabetes risk, with the threshold close to 20.5µg/L and 75.9µg/L, respectively (both P for overall &lt; 0.05; both P for non-linearity &lt; 0.05). (2) There were L-shaped associations of rubidium and lead with diabetes risk, with the turning point close to 144.5µg/L and 2.5µg/L, respectively (both P for overall &lt; 0.05; both P for non-linearity &lt; 0.05). (3) Manganese was linearly and negatively correlated with diabetes risk when concentrations of manganese were less than approximately 4.2 μg/L (P for overall &lt; 0.05; P for non-linearity = 0.268). The BKMR model also revealed a negative combined effect of metal mixtures on diabetes risk and potential interactions between six pairs of metals (aluminium-manganese, aluminium-selenium, aluminium-rubidium, aluminium-lead, manganese-selenium, and manganese-rubidium). In summary, we need to pay attention to the role of low plasma levels of aluminium, selenium, manganese, rubidium, and lead in diabetes, especially regarding their safety windows.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"292 ","pages":"Article 117941"},"PeriodicalIF":6.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of xylene as a nematicide formulation and its synergistic effects with abamectin in the management of pine wood nematodes","authors":"Min-Kyoung Kang ,&nbsp;Hyeon-Ji Kim ,&nbsp;Jong-Hoon Kim","doi":"10.1016/j.ecoenv.2025.117965","DOIUrl":"10.1016/j.ecoenv.2025.117965","url":null,"abstract":"<div><div>Pine wilt disease (PWD), caused by the pine wood nematode, poses a significant global threat to forests, resulting in severe economic and environmental damage. Currently, managing the occurrence of PWD in plants remains an ongoing challenge due to its multiple modes of transmission and broad adaptability. Moreover, there are only a few nematicidal agents for controlling these harmful nematodes. Therefore, the identification of novel nematicidal agents has become urgent and is of critical practical and economic significance. This study aimed to evaluate xylene as a supplementary agent in managing pine wood nematodes. The nematicidal efficacy of xylene was assessed, revealing that it effectively suppresses the growth, reproduction, and behavior of <em>Bursaphelenchus xylophilus</em> at certain concentrations. Notably, the combination of xylene and abamectin achieved a 100 % mortality rate at a significantly lower concentration of 0.5 µg/mL, approximately eight times less than abamectin alone. In pot experiments, xylene treatment did not exhibit phytotoxicity towards pine trees, confirming its nematicidal activity. Furthermore, the xylene-abamectin combination effectively inhibited the development of PWD in 5-year-old <em>Pinus densiflora</em> trees at a dosage of 0.45 mg per tree, roughly 8 times lower than the required amount of abamectin alone under greenhouse conditions. This study is the first to demonstrate the nematicidal effects of xylene, suggesting that xylene could serve as an effective agent in nematode control formulations.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"292 ","pages":"Article 117965"},"PeriodicalIF":6.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triple combination exposure to MPs, Pb2+ and As3+ induces ferroptosis at environmentally relevant concentrations in early development of zebrafish","authors":"Yue Cao ,&nbsp;Xiangao Yao ,&nbsp;Yuanren Zhu ,&nbsp;Yue Lu ,&nbsp;Rui Ding ,&nbsp;Shensheng Xiao ,&nbsp;Qiao Wang ,&nbsp;Sheng Wen ,&nbsp;Xin Liu ,&nbsp;Zhiyong Gong ,&nbsp;Min Fang ,&nbsp;Xiaole Zhao","doi":"10.1016/j.ecoenv.2025.117942","DOIUrl":"10.1016/j.ecoenv.2025.117942","url":null,"abstract":"<div><div>There remains a substantial knowledge gap in understanding the coexistence effects of Microplastics (MPs), lead (Pb) and arsenic (As), which are ubiquitous environmental contaminants. Here, zebrafish (<em>Danio rerio</em>) embryos were used to investigate the impact of triple combined exposure to MPs (50 μg/L), Pb²⁺ (10 μg/L) and As³⁺ (200 μg/L) on the developmental responses. Survival and hatching rates were notably reduced to 32.7 % and 58.8 %, respectively. Meanwhile, the frequency of spontaneous tail contractions increased by 8.1 %, whereas heart rate and body length decreased by 4.4 % and 5.1 %, respectively. These findings demonstrated that the triple exposure markedly disrupted developmental processes and altered behavioral profiles in zebrafish larvae. Furthermore, 16 S rRNA sequencing revealed that the metabolic processes of glutathione and xenobiotics, as well as intracellular iron transport, were significantly impacted, triggering ferroptosis in the larvae exposed to triple combination. Collectively, the co-exposure to MPs, Pb²⁺ and As³⁺ even at low concentrations could significantly disrupt the developmental progress and biological functioning during the early stages of zebrafish. This will help guide future comprehensive studies on the impact of triple combined exposure during early developmental stages.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"292 ","pages":"Article 117942"},"PeriodicalIF":6.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AFB1 exposure promotes SIV replication and lung damage via RIG-I- and p38-mediated RETREG1/FAM134B-dependent endoplasmic reticulum autophagy","authors":"Wenshuo Zhao ,&nbsp;Siyao Pang ,&nbsp;Jinlong Zhang ,&nbsp;Zhaoran Yao ,&nbsp;Yuqi Song ,&nbsp;Yuhang Sun","doi":"10.1016/j.ecoenv.2025.117970","DOIUrl":"10.1016/j.ecoenv.2025.117970","url":null,"abstract":"<div><div>Aflatoxin B1 (AFB1) contamination is common worldwide and highly harmful to humans and animals. Our previous studies suggested that AFB1 exposure promotes the replication of H1N1 swine influenza virus (SIV). However, its mechanism is not clear. Here, TCID₅₀, qRT-PCR, and WB assays were used to detect SIV replication, after which proteomic detection was used to screen key proteins and pathways. Thirty piglets were subsequently randomly divided into 6 groups. The low-pathogenicity SIV was inoculated to establish a piglet model of SIV infection. Different doses of AFB1 were administered daily to SIV-infected piglets for 14 d. The <em>in vitro</em> results revealed that 0.02–0.04 μg/mL AFB1 markedly promoted SIV replication. Proteomic analysis revealed that reticulophagy regulator 1 (RETREG1/FAM134B) and p38 signaling were markedly upregulated, whereas RIG-I signaling was significantly downregulated. The above results were confirmed by qRT-PCR and WB assays. Transmission electron microscopy was used to further prove that AFB1 promoted endoplasmic reticulum autophagy (ER-phagy) in SIV-infected PAMs. RIG-I activator and p38 inhibitor reversed the upregulation of RETREG1 and AFB1-promoted SIV replication, and RETREG1 inhibitor reversed the AFB1-promoted SIV replication. <em>In vivo</em> experiments confirmed that AFB1 upregulated RETREG1 and p38, downregulated RIG-I, and promoted SIV replication and lung damage. Taken together, our results reveal that AFB1 promotes SIV replication and lung damage via RIG-I- and p38-mediated RETREG1/FAM134B-dependent ER-phagy and suggest the therapeutic potential of RETREG1-, RIG-I-, and p38-related drugs for influenza. Our findings also provide insights into why the occurrence of other infectious diseases is increasing.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"292 ","pages":"Article 117970"},"PeriodicalIF":6.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between serum metal mixtures and systemic inflammation indices among Chinese early adolescents: A prospective cohort study","authors":"Yonghan Li ,&nbsp;Binbin Huang ,&nbsp;Mengyuan Yuan ,&nbsp;Chao Zhang ,&nbsp;Xueying Zhang ,&nbsp;Jiahu Hao ,&nbsp;Fangbiao Tao ,&nbsp;Feng Geng ,&nbsp;Gengfu Wang ,&nbsp;Puyu Su","doi":"10.1016/j.ecoenv.2025.117952","DOIUrl":"10.1016/j.ecoenv.2025.117952","url":null,"abstract":"<div><h3>Background</h3><div>Research has demonstrated a link between metal exposure and inflammation. However, little is known about this relationship among adolescents, especially in prospective cohort studies. The aim of this study was to investigate the relationship between serum metal exposure and inflammatory status in Chinese early adolescents.</div></div><div><h3>Methods</h3><div>In this study, 12 serum metals were detected at baseline in 1551 participants from the Chinese Early Adolescents Cohort. The participants' inflammatory status was assessed via three systemic inflammation indices (neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII)) at both baseline and follow-up. Generalized linear mixed models and restricted cubic splines regression were used to examine the linear and nonlinear relationships between single metal concentrations and systemic inflammation indices. Multiple mixture models were implemented to assess the relationships of mixed metals with systemic inflammation indices. Additionally, sex subgroup analyses were conducted to explore the sex-specific associations between serum metals and inflammatory status.</div></div><div><h3>Results</h3><div>Single-exposure analysis revealed that exposure to multiple serum metals, such as chromium, cobalt, copper and lead, was positively associated with the NLR and SII, whereas iron was negatively correlated with the three systemic inflammation indices (<em>P</em>_FDR&lt;0.05). Additionally, inverted U-shaped associations were observed between vanadium, manganese and systemic inflammation indices. According to the mixture models, high levels of the serum metal mixture were positively correlated with the NLR and the SII. Cobalt had the highest positive weight in the mixed samples, whereas iron had the greatest negative weight in the serum-metal mixtures. Subgroup analyses revealed that serum exposure to the metal mixture had a more significant effect on systemic inflammation markers in females than in males.</div></div><div><h3>Conclusions</h3><div>This study reveals the impact of real-world mixed metal exposure on adolescents’ inflammatory levels, which is of primary significance for protecting the healthy development of early adolescents.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"292 ","pages":"Article 117952"},"PeriodicalIF":6.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short-term subacute di(2-ethylhexyl) phthalate exposure disrupts gut microbiota, metabolome, liver transcriptome, immunity, and induces liver injury in rats","authors":"Qian Li ,&nbsp;Yaqi Zhang ,&nbsp;Hua Zha,&nbsp;Lvwan Xu,&nbsp;Yuanshuai Su,&nbsp;He Jiang,&nbsp;Lanjuan Li","doi":"10.1016/j.ecoenv.2025.117948","DOIUrl":"10.1016/j.ecoenv.2025.117948","url":null,"abstract":"<div><div>Di(2-ethylhexyl) phthalate (DEHP) is recognised as a pollutant with multiple health risks. In this study, multi-omics approaches were used to examine the alterations in immunity, gut microbiota and metabolome, and liver transcriptome in the rats with DEHP-induced subacute liver injury. Following short-term subacute DEHP exposure, the rats exhibited decreased body weight, increased liver weight, impaired liver function and immunity, and signs of liver injury. DEHP exposure reduced the richness, diversity, and evenness of gut microbiota, resulting in elevated levels of <em>Lactobacillus</em>, <em>Romboutsia</em>, and <em>Alistipes</em> and decreased levels of <em>unclassified Muribaculaceae</em>, <em>Oscillibacter</em>, and <em>Akkermansia</em> in the intestine. Multiple gut metabolic pathways were altered by DEHP, among which sphingolipid metabolism was enriched with the most differentially expressed metabolites. In the liver tissues of rats exposed to DEHP, lipid metabolism-related pathways were altered, including downregulated steroid biosynthesis and upregulated fatty acid degradation. In conclusion, the relevant findings suggest that DEHP can cause immune alteration, gut microbiota dysbiosis, gut metabolome disruption, liver transcriptome dysregulation, and result in liver injury in rats. These results could benefit the clinical diagnosis of DEHP-induced subacute liver injury.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"292 ","pages":"Article 117948"},"PeriodicalIF":6.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging per- and polyfluoroalkyl substance perfluoro-(3,5,7,9-tetraoxadecanoic) acid (PFO4DA) impairs steroidogenesis and spermatogenesis by suppressing StAR and CYP11A1 expression in mice","authors":"Lutefei Mutalifu ,&nbsp;Wei Xie ,&nbsp;Danyang Wang ,&nbsp;Mengxue Zhi ,&nbsp;Yong Guo ,&nbsp;Jianshe Wang","doi":"10.1016/j.ecoenv.2025.117962","DOIUrl":"10.1016/j.ecoenv.2025.117962","url":null,"abstract":"<div><div>Perfluoroalkyl ether carboxylic acids (PFECA) represent an important group of emerging per- and polyfluoroalkyl substances (PFAS). PFECA have been found in a variety of environmental matrices. While legacy PFAS have been extensively documented for their reproductive toxicity, the health implications of emerging alternatives like PFECA remains unclear. The present study is aimed at investigating the potential reproductive toxicity of perfluoro-(3,5,7,9-tetraoxadecanoic) acid (PFO4DA), a type of PFECA, through combining <em>in vivo</em> and <em>in vitro</em> assays. Adult male BALB/c mice were exposed to 2 and 10 mg/kg body-weight/day of PFO4DA via oral gavage for four consecutive weeks. While no overt structural or morphological changes were observed in the testes following PFO4DA exposure, significant reductions in both sperm quantity and quality were evident, correlating with increased PFO4DA dosage. PFO4DA exposure compromised the integrity of the blood-testis barrier (BTB) and led to a moderate decrease in BTB-associated junction proteins, including Connexin-43 and Claudin-11. Notably, PFO4DA disrupted androgen production, resulting in a significant reduction in testosterone (T) levels (&gt; 60 %) in both serum and testicular tissue. Mechanistic analysis revealed that PFO4DA significantly repressed the expression levels of steroidogenic genes StAR and CYP11A1 both in testes and in cultured Leydig cells (TM3). These findings suggest that PFO4DA primarily targets the steroidogenic pathway in Leydig cells by suppressing StAR and CYP11A1, thereby inhibiting T synthesis. The subsequent T deficiency impairs Sertoli cell function and BTB integrity, ultimately disrupting spermatogenesis and impacting male reproductive health.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"292 ","pages":"Article 117962"},"PeriodicalIF":6.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}