Cell Biology and Toxicology最新文献

{"title":"SerpinB1a induces hepatopulmonary syndrome by promoting CTSG/AMPK/mTOR pathway-mediated mitophagy.","authors":"Liang Li, Jianzhong Li, Wendeng Li, Yuefeng Ma, Shaomin Li","doi":"10.1007/s10565-025-10082-y","DOIUrl":"10.1007/s10565-025-10082-y","url":null,"abstract":"<p><p>Mitophagy, as an important mechanism for selective removal of damaged mitochondria in cells, plays a crucial role in upholding cellular homeostasis. Mounting evidence suggests that autophagy is associated with lung disease. However, the potential molecular mechanisms affecting mitophagy are still obscure in hepatopulmonary syndrome (HPS) development. In this study, elevated SerpinB1a levels were detected in HPS patients' serum, showing a significant inverse correlation with arterial oxygen saturation. In the CBDL-induced rat HPS model, SerpinB1a knockdown attenuated pulmonary hemorrhage, microvascular dilation, and hepatic fibrosis. In vitro studies demonstrated that treatment of PMVECs with serum from HPS rats induced pathological proliferation, migration, and angiogenesis. Silencing of SerpinB1a effectively suppressed these aberrant cellular processes. Mechanistically, SerpinB1a promoted PMVEC dysfunction by interacting with and upregulating Cathepsin G (CTSG), thus activating the VEGF / AMPK / mTOR pathway and subsequent induction of mitophagy. In conclusion, SerpinB1a knockdown attenuated pulmonary microvascular dilation and HPS progression by inhibiting this CTSG/VEGF/AMPK/mTOR axis. These findings elucidate the mechanistic role of SerpinB1a in HPS progression and suggest its potential as a novel therapeutic target for HPS.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"142"},"PeriodicalIF":5.9,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ETV4 promotes ovarian cancer growth by regulating mitochondrial function through Mfn2 ubiquitination mediated by the E3 ubiquitin ligase MARCH9.","authors":"Ying Wang, Zhan Wang, Juan Chen, Li Cai, Xia Luo, Nayiyuan Wu","doi":"10.1007/s10565-025-10094-8","DOIUrl":"10.1007/s10565-025-10094-8","url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial dysfunction affects the development of ovarian cancer (OC). ETV4 is involved in mitochondrial fusion. The regulatory pathways of ETV4 in OC cells have not been further investigated. In this study, we aimed to explore the effects of ETV4 on OC development and analyze the downstream regulatory pathways of ETV4.</p><p><strong>Methods: </strong>The expression of ETV4 in OC cell lines (SK-OV-3, HEY, A2780, and OVCAR-3) was verified. After silencing ETV4, indicators related to mitochondrial function, including ATP level, mitochondrial membrane potential, mitochondrial DNA (mtDNA), and mitochondrial ROS (mtROS), were analyzed. The expression of mitochondrial fission/fusion-related markers (Mfn1, Mfn2, OPA1, DRP1, MFF, and FIS1) was detected. In vivo experiments were used to verify the effect of ETV4 on OC development.</p><p><strong>Results: </strong>The TCGA-OV data indicated that ETV4 was highly expressed in OC. Silencing ETV4 inhibited the proliferation of OC cells. Mitochondrial membrane potential and ATP levels increased after ETV4 silencing, while mtDNA and mtROS levels decreased. ETV4 silencing promoted Mfn2 protein expression but did not affect Mfn2 mRNA level. Mfn2-associated E3 ubiquitin ligase MARCH9 was targeted and regulated by ETV4. MARCH9 overexpression alleviated the regulation of ETV4 silencing on mitochondrial function in OC cells. Lysosomal inhibitor CQ blocked the degradation of ubiquitinated Mfn2 protein. MARCH9 was found to mediate robust ubiquitination of Mfn2 via the K63-linked ubiquitination.</p><p><strong>Conclusions: </strong>ETV4 was highly expressed in OC and involved in the regulation of mitochondrial function. ETV4 regulated Mfn2 ubiquitination linked by K63 by regulating MARCH9.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"141"},"PeriodicalIF":5.9,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145328342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PARP1 contributes to intimal hyperplasia by regulating METTL3-mediated m6A methylation of TRAIL.","authors":"Shaodong Li, Fengxiang Pang, Wenhai Guo, Weibing Guan","doi":"10.1007/s10565-025-10076-w","DOIUrl":"10.1007/s10565-025-10076-w","url":null,"abstract":"<p><p>Poly (ADP-ribose) polymerase 1 (PARP1) promotes vascular intimal hyperplasia (IH) while contributing to N6-methyladenosine (m6A) methylation regulatory processes. The present study focuses on whether the PARP1 inhibitor PJ34 can improve vascular IH by regulating m6A methylation modification. Mice with femoral artery wire injury-induced IH and platelet-derived growth factor-BB (PDGF-BB)-challenged mouse vascular smooth muscle cells (VSMCs) were utilized in the study. PJ34 treatment significantly alleviated neointimal formation, suppressed VSMC proliferation and phenotypic switching, and reduced global m6A methylation and methyltransferase-like 3 (METTL3) expression in injured arteries. Dot blot, RT-qPCR, western blot, and immunohistochemistry confirmed these changes. In vitro, PJ34 impaired PDGF-BB-stimulated proliferation and migration in VSMCs, effects reversed by METTL3 overexpression but not observed in METTL3-deficient cells. Mechanistically, METTL3 regulated the m6A methylation and stability of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mRNA. PJ34 downregulated TRAIL expression via inhibition of METTL3-mediated m6A modification. TRAIL-knockout mice were resistant to the vascular protective effects of PJ34, highlighting the essential downstream role of TRAIL. Immunohistochemistry confirmed TRAIL localization in the neointima and media. Moreover, TRAIL deficiency did not lead to increased systemic inflammation, as TNF-α, IL-6, and IL-1β levels in plasma remained unchanged. In conclusion, PJ34 mitigates vascular IH by modulating METTL3-mediated TRAIL m6A methylation. This finding provides novel insight into epigenetic therapy for vascular remodeling.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"140"},"PeriodicalIF":5.9,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12532763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145298740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginsenoside Rh2 targets SIRT1-mediated deacetylation to modulate ERα/AR balance and overcome endocrine therapy resistance in prostate cancer using 3D organoid models.","authors":"Xinan Chen, Wei Luo, Yueying Ren, Zezhong Mou, Chenyang Xu, Jimeng Hu, Mengbo Hu, Haowen Jiang","doi":"10.1007/s10565-025-10091-x","DOIUrl":"10.1007/s10565-025-10091-x","url":null,"abstract":"<p><p>Resistance to endocrine therapy remains a major challenge in treating prostate cancer (PCa), highlighting the need for alternative therapeutic approaches. In this study, we investigated the potential of Ginsenoside Rh2 to counteract such resistance by influencing the SIRT1-dependent deacetylation pathway, thereby modulating the equilibrium between estrogen receptor α (ERα) and androgen receptor (AR). We proposed that Rh2 may suppress therapy-resistant PCa progression by adjusting ERα/AR transcriptional dynamics. Through network pharmacology analysis, key anti-PCa targets of Rh2 were identified, with Cytoscape enrichment indicating a pivotal role in AR signaling modulation. Functional validation was performed using 3D tumor organoids and human PCa cell lines (C4-2B and LNCaP) treated with Rh2 to assess cellular behaviors and receptor deacetylation status. Additionally, xenograft mouse models were employed to evaluate Rh2's in vivo effects, based on tumor burden, serum PSA levels, and tissue histopathology. Rh2 treatment led to significant, dose- and time-dependent inhibition of PCa cell proliferation and metastatic traits, accompanied by restored ERα/AR balance through activation of SIRT1. In animal studies, Rh2 notably reduced tumor size, decreased PSA expression, and improved systemic health indicators. Collectively, our results suggest that Rh2 re-sensitizes PCa to endocrine therapy by targeting the SIRT1 pathway, positioning it as a promising phytochemical candidate for managing resistant PCa. This work provides mechanistic insights supporting Rh2's potential for clinical translation.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"139"},"PeriodicalIF":5.9,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12528294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Innovating non‑small cell lung cancer treatment with novel TM‑GL/NPs nanoparticles for Glycitin delivery.","authors":"Chang Liu, Jiabao Zhao, Jun Liu, Yudong Wang","doi":"10.1007/s10565-025-10108-5","DOIUrl":"10.1007/s10565-025-10108-5","url":null,"abstract":"","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"138"},"PeriodicalIF":5.9,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12513919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of SPTLC2 as a key driver promoting microglial activation and energy metabolism reprogramming after ischemic stroke through bulk and single-cell analyses combined with experimental validation.","authors":"Yongxing Lai, Peiqiang Lin, Zhiyun Wu, Tin Chen, Wenyao Hong, Mouwei Zheng, Jianhao Chen, Nan Liu, Hongbin Chen","doi":"10.1007/s10565-025-10085-9","DOIUrl":"10.1007/s10565-025-10085-9","url":null,"abstract":"<p><strong>Background: </strong>Ischemic stroke (IS) stands as a principal contributor to high rates of sickness and death. The condition's pathological development is complicated, featuring mechanisms like mitochondrial impairment and the activation of microglial cells. A thorough grasp of these intricate processes is vital for creating successful treatment strategies.</p><p><strong>Methods: </strong>We applied Weighted Gene Co-expression Network Analysis (WGCNA) to find gene sets with a strong correlation to IS. Integrated machine learning approachs were used to identify key mitochondrial-related genes (MRGs). From this analysis, SPTLC2 was identified as a pivotal MRG and was subsequently analyzed in detail using single-cell RNA sequencing (scRNA-seq) datasets. We performed functional confirmation using experimental stroke simulations, which included transient middle cerebral artery occlusion (tMCAO) in mice and in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) on primary microglia.</p><p><strong>Results: </strong>WGCNA revealed two critical modules (yellow and blue) comprising 5348 genes, which were predominantly enriched in immune response, nerve regeneration, and lipid metabolism. We exhibited the robust and superior performance of MRGs in stroke prediction, which contributed to an optimal combination of ridge regression and random forest fitted on 18 MRGs. Subsequently, elevated expression of the SPTLC2 gene was observed in microglia following stroke. Functional studies and experimental validation demonstrated that SPTLC2 promoted microglial pro-inflammatory phenotype, metabolic reprogramming towards glycolysis, and exacerbated cell-cell communication alterations. SPTLC2-specific knockdown in myeloid cells using an adeno-associated virus (AAV) in our tMCAO model alleviated neurobehavioral deficits, reduced infarct volume, and improved mitochondrial function by elevating oxidative stress and mitigating mitochondrial membrane potential depolarization. Additionally, SPTLC2 was regulated by the transcription factor FLI1, and molecular docking identified potential drugs targeting SPTLC2, including Nystatin A3, Moxidectin, and Lumacaftor.</p><p><strong>Conclusion: </strong>Our study highlights SPTLC2 as a critical mediator of microglial activation and metabolic reprogramming in ischemic stroke, providing a foundation for developing novel therapeutic strategies targeting SPTLC2 to improve stroke outcomes.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"137"},"PeriodicalIF":5.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12504400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Skp2 by Tanshinone IIA overcomes chemoresistance in colorectal cancer.","authors":"Xin Dong, Kexin Li, Ruirui Wang, Baojun Wei, Yiling Li, Yu Zhang, Shengkai Huang, Guojing Wang, Quanquan Gao, Wei Li, Wei Cui","doi":"10.1007/s10565-025-10084-w","DOIUrl":"10.1007/s10565-025-10084-w","url":null,"abstract":"<p><p>Fluorouracil (5-Fu)-based chemotherapy is a first-line treatment option for advanced colorectal cancer (CRC). However, long-term use of 5-Fu often leads to chemoresistance, which limits its therapeutic efficacy, highlighting the need for developing novel regimens to improve CRC treatment outcomes. In this study, we found that Tan IIA inhibits aerobic glycolysis in CRC cells via suppressing Skp2/Akt/HK2 signaling axis and thereby overcomes 5-Fu resistance. Specifically, Tan IIA induces ubiquitination-mediated Skp2 degradation by attenuating the interaction between USP2 and Skp2. Moreover, the combination of Tan IIA with USP2 inhibitor ML364 overcomes 5-Fu resistance in vitro and xenograft mouse models. This study elucidates a novel mechanism of 5-Fu resistance and offers a promising combination treatment option for overcoming chemoresistance.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"135"},"PeriodicalIF":5.9,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in mitochondria-nucleus crosstalk in septic cardiomyopathy.","authors":"Wei Chen, Zeze Zhao, Zhengguang Geng, Han Zhang, Xiaoyun Fu","doi":"10.1007/s10565-025-10090-y","DOIUrl":"10.1007/s10565-025-10090-y","url":null,"abstract":"<p><p>Sepsis-induced cardiomyopathy (SICM), a critical contributor to the high mortality rate associated with sepsis, involves complex pathophysiological mechanisms that remain incompletely elucidated. In recent years, dysregulation of bidirectional signaling communication between mitochondria and the nucleus has been recognized as a pivotal factor in the pathogenesis of SICM. The anterograde signaling pathways-including the PGC-1α/NRF1/NRF2 axis, SIRT3-mediated deacetylation, and TFAM-dependent mitochondrial DNA (mtDNA) maintenance-are suppressed by inflammation and metabolic disturbances. This suppression leads to impaired mitochondrial biogenesis and disrupted energy metabolism. Concurrently, within retrograde signaling pathways, molecular mediators such as reactive oxygen species (ROS), mtDNA, and calcium signaling activate pro-inflammatory and apoptotic pathways, notably NF-κB and cGAS-STING. This activation establishes a vicious cycle perpetuating inflammation and cellular damage. Although current targeted interventions aimed at modulating mitochondrial-nuclear crosstalk have demonstrated some efficacy in animal models, their clinical translation faces significant challenges. These include the dynamic nature of the disease, substantial interindividual variability, and difficulties in achieving targeted delivery. This review summarizes the mechanisms of mitochondrial-nuclear bidirectional signaling in SICM and explores potential therapeutic targets, aiming to provide novel insights for SICM treatment strategies.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"136"},"PeriodicalIF":5.9,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased reactive astrocytes in hippocampal CA1 region mediated by decreased CXCR7 is involved in postoperative cognitive dysfunction in aged mice.","authors":"Qiang Liu, Chen-Rui Zhou, Hai-Bi Wang, Yan-Ping Liu, Wei Dong, Jie Wan, Hui-Hui Miao, Cheng-Hua Zhou, Yu-Qing Wu","doi":"10.1007/s10565-025-10083-x","DOIUrl":"10.1007/s10565-025-10083-x","url":null,"abstract":"<p><p>Postoperative cognitive dysfunction (POCD) is a prevalent neurological complication that significantly impairs recovery in elderly surgical patients. While astrocyte activation has been implicated in various neurodegenerative disorders, its dynamic changes and precise role in POCD pathogenesis remain poorly understood. In this study, we observed selective activation of astrocytes (but not microglia) in the hippocampal CA1 region of POCD model mice at postoperative day 3, accompanied by marked downregulation of the atypical chemokine receptor CXCR7. Notably, both astrocyte-specific CXCR7 overexpression in the hippocampal CA1 region and systemic administration of the CXCR7 agonist AMD3100 effectively attenuated astrocyte activation, reduced neuroinflammation, and significantly improved synaptic plasticity and cognitive performance in aged surgical mice. Furthermore, chemogenetic inhibition of hippocampal astrocytes during the perioperative period similarly ameliorated neuroinflammatory responses and cognitive deficits. Our findings demonstrate that surgery induces reactive astrogliosis in the hippocampal CA1 region through CXCR7 downregulation, ultimately leading to synaptic dysfunction and cognitive impairment. These results identify CXCR7 as a promising therapeutic target for POCD prevention.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"133"},"PeriodicalIF":5.9,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"scRNA-seq deciphers molecular mechanisms of endocrine disruptor 4-nonylphenol impairing spermatogenesis in mice.","authors":"Xue Zhao, Yanan Tian, Dan Zhou, Xiaojuan Tang, Xiaoyang Zhou, Xuelin Wang, Yan He, Pengxia Yu, Jiaolong Huang, Yan Tan, Peng Duan","doi":"10.1007/s10565-025-10095-7","DOIUrl":"10.1007/s10565-025-10095-7","url":null,"abstract":"<p><p>4-Nonylphenol (NP) is an environmental endocrine disruptor widely used in consumer products. Previous studies have shown that NP can interfere with hormone synthesis and metabolism in humans and animals, leading to male reproductive dysfunction. This study utilized the scRNA-seq method to evaluate cell populations and their heterogeneity, aiming to elucidate the toxic mechanisms of NP exposure on testicular cells. We demonstrate, for the first time, the transcriptomic characteristics of testicular single cells in adolescent mice exposed to NP. Adolescent mice, initially exposed at 4 weeks of age, were subsequently analyzed at sexual maturity after a continuous exposure period of 3 months. The blank control and NP-exposed groups underwent scRNA-seq analysis, identifying ten cell populations. The results showed that after NP exposure, the number of germline cells was remarkably reduced compared to the control group. NP exposure significantly decreased the protein expression of the four common differentially expressed genes (DEGs) (Cmtm2b, Rpl28, Adam32, and Pgam2). The DEGs enriched in the GO functions of the four germline cell types were spermatogenesis and spermatid development. KEGG analysis showed that the DEGs were enriched in the oxidative phosphorylation, and ROS signaling pathways. Further analysis of intercellular interactions revealed that NP exposure altered intercellular communication between germ cells, with the NECTIN3-NECTIN2 receptor-ligand interactions activating between spermatogonia, Sertoli, and Leydig cells. Germ cells bind to Sertoli and Leydig cells via NECTIN3-NECTIN2 receptor ligands. Somatic cells bind to RS and ES through GRN-SORT1 receptor ligands. CADM1-CADM1 receptor-ligand interactions enhances between germ and Sertoli cells. Our study provides new insights into the potential impacts of NP on spermatogenesis and sperm function, emphasizing the importance of environmental hormones in male fertility issues.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"134"},"PeriodicalIF":5.9,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}