BMC Biology最新文献

{"title":"doc2a and doc2b contribute to locomotor and social behaviors by down-regulating npas4b in zebrafish.","authors":"Yali Chi, Tao Feng, Zixin Du, Ping Huang, Wenjun Yu, Haihua Liu, Wanshan Wang, Xinping Yang, Liping Huang","doi":"10.1186/s12915-025-02224-9","DOIUrl":"10.1186/s12915-025-02224-9","url":null,"abstract":"<p><strong>Background: </strong>Copy number variations (CNVs) occurring on chromosome 16p11.2 are associated with various neurodevelopmental disorders, including autism spectrum disorder (ASD), schizophrenia, and intellectual disability. Among the genes situated within the critical CNV region, DOC2A is noteworthy. We generated frameshift mutations in doc2a (double C2-like domain-containing protein a) and its paralog doc2b (double C2-like domain-containing protein b) in zebrafish via CRISPR-Cas9 respectively and obtained double-mutant doc2a^-/-doc2b^-/- by mating the single-mutant doc2a^+/+doc2b^-/- and doc2a^-/-doc2b^+/+ zebrafish.</p><p><strong>Results: </strong>doc2a^-/-doc2b^-/- mutants displayed aberrant morphology including tail bending and deformity, and morphologically normal individuals displayed aberrant behaviors, including reduced locomotion activity, impaired social interaction, and irregular movements. Whole-brain transcriptome sequencing of both wild-type and doc2a^-/-doc2b^-/- mutants revealed differentially expressed genes (DEGs) enriched with ASD candidate genes and synaptic signaling pathways, notably down-regulated gene npas4b (Neuronal PAS domain protein 4b). We found the downstream targets of the transcription factor Npas4b in the DEGs were mostly enriched in the synaptic signaling pathways. The npas4b knockout and knockdown zebrafish showed reduced locomotion activity and impaired social interaction similar to the behaviors observed in doc2a^-/-doc2b^-/- mutants.</p><p><strong>Conclusions: </strong>This study suggests that DOC2A in the critical region of 16p11.2 may contribute to the pathogenesis of autism by interacting with other genes, such as DOC2B, and that the downregulation of NPAS4 may play an important role in autism.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"167"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"stGRL: spatial domain identification, denoising, and imputation algorithm for spatial transcriptome data based on multi-task graph contrastive representation learning.","authors":"Xin Lu, Murong Zhou, Bo Gao, Fang Wang, Shuilin Jin, Qiaoming Liu, Guohua Wang","doi":"10.1186/s12915-025-02290-z","DOIUrl":"10.1186/s12915-025-02290-z","url":null,"abstract":"<p><strong>Background: </strong>Spatial transcriptomics now enables sequencing while preserving the spatial location of cells. This significantly enhances researchers' understanding of cellular and tissue functions in their spatial context. However, due to current technical limitations, spatial transcriptomics data often exhibit high dropout rates and noise, posing challenges for downstream analysis, like spot clustering, differential gene analysis, and spatial domain identification. To address those challenges, we propose stGRL, a novel deep multi-task graph neural network model tailored for spatial transcriptomics. stGRL employs an encoder-decoder architecture with a zero-inflated negative binomial (ZINB) distribution to reconstruct input data while effectively addressing dropout events. Additionally, it integrates graph contrastive representation learning to enhance the consistency of node embeddings, thereby improving clustering performance.</p><p><strong>Results: </strong>Through benchmark experiments on various spatial transcriptomics datasets, stGRL demonstrated a superior ability to identify spatial features compared to current mainstream methods. In-depth analyses reveal that the denoised data generated by stGRL not only preserves the spatial hierarchy of tissues but also accurately identifies differentially expressed genes. When applied to breast cancer datasets, stGRL effectively analyzed the differences between cancerous regions and carcinoma in situ areas, uncovering that carcinoma in situ regions are predominantly regulated by the immune system, which limits cancer cell development through inflammatory responses. Additionally, in the spatial transcriptomics analysis of ovarian cancer, stGRL successfully annotated cell types, accurately identified B cell-enriched regions, and discovered a novel target gene, MZB1, with potential therapeutic value.</p><p><strong>Conclusions: </strong>stGRL is an effective method for integrating multiple tasks in spatial transcriptome analysis. Our study highlights its broad applicability and outstanding performance in analyzing spatial transcriptome data. This method offers a powerful analytical tool for uncovering the spatial heterogeneity of complex tissues and identifying potential therapeutic targets for disease.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"177"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid metabolites affected by deficient autophagy antagonize the occurrence of autophagy through AMPK signaling in insects.","authors":"Ling Tian, Qien Zhong, Yubei Yang, Wenmei Wu, Yang Xiao, Sheng Li, Kang Li","doi":"10.1186/s12915-025-02274-z","DOIUrl":"10.1186/s12915-025-02274-z","url":null,"abstract":"<p><strong>Background: </strong>Autophagy is essential for removing damaged organelles and intracellular materials as well as invasive pathogens. The autophagic degradation of intracellular lipids plays a key role in maintaining cellular homeostasis. However, the mechanism of lipid metabolism regulated by autophagy, as well as whether or how lipid metabolites affect autophagy, remain unclear.</p><p><strong>Results: </strong>RNAi of the key autophagy-related (Atg) genes, notably Atg1 and Atg8, suppressed autophagy, while overexpression of these Atg genes facilitated lipid degradation in both Bombyx mori and Drosophila melanogaster. In addition, disrupting autophagosome-lysosome fusion by chloroquine treatment inhibited lipid degradation during both metamorphosis and starvation. LC-MS/MS analysis showed that overexpression of DmAtg1:DmAtg13 mainly degraded glycerolipids, while DmAtg1 mutation predominantly accumulated glycerophospholipids. Notably, the significantly upregulated GPs following autophagy blockage, including C24H50NO7P (LPE, 19:0), C25H52NO7P (LPC, 0:0/17:0), C27H56NO7P (LPC, 0:0/19:0), and C28H58NO7P (LPC, 20:0/0:0), exerted a suppressive effect on autophagy occurrence mainly through the downregulation of AMPK signaling.</p><p><strong>Conclusions: </strong>Autophagosome and autolysosome formations are both critical for lipid degradation. Conversely, the metabolites accumulated due to dysfunctional autophagy inhibit autophagy occurrence by downregulation of AMPK signaling, thereby forming a regulatory loop in insects. Collectively, our results provide valuable insights into applications for beneficial insects and pest management, while also present potential chemicals applied on human diseases related to autophagy or lipid metabolism.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"193"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-dimensional annotation of porcine variants using genomic and epigenomic features in pigs.","authors":"Hongwei Yin, Liu Yang, Qianyi Zhao, Wenye Yao, Jinyan Teng, Yahui Gao, Zhiting Xu, Qing Lin, Shuqi Diao, Xiaohong Liu, Fuping Zhao, Zhongyin Zhou, Qishan Wang, Jiaqi Li, Zhe Zhang, Huaijun Zhou, Martien A M Groenen, Ole Madsen, Lijing Bai, Dailu Guan, Lingzhao Fang, Kui Li","doi":"10.1186/s12915-025-02279-8","DOIUrl":"10.1186/s12915-025-02279-8","url":null,"abstract":"<p><strong>Background: </strong>Investigating the functional impact of genomic variants is essential to uncover the molecular mechanisms behind complex traits. This study compiled a comprehensive dataset of 1,817 whole-genome sequences from diverse pig breeds and populations, capturing the global pig genetic diversity.</p><p><strong>Results: </strong>Our analyses first revealed 27,167 loss-of-function variants (LoFs), the majority of which also influenced gene expression and splicing, and enriched in genomic regions associated with complex traits in pigs. We further genome-wide annotated non-coding variants, and then focused on these resided in 5' untranslated region (5'UTR). Although they had lower deleterious impact on protein sequence compared to coding variants, they enriched in promoters and exhibited functional consequences on gene expression and splicing and finally complex traits. We employed the Basenji deep learning model and ATAC-seq to predict the impact of these SNPs on chromatin accessibility in 13 pig tissues. SNPs with higher predicted scores demonstrated stronger effects on gene expression/splicing and complex traits-particularly average backfat thickness-compared to variants with lower scores.</p><p><strong>Conclusions: </strong>In summary, our study provides a comprehensive catalog of genomic variants in both protein-coding and non-coding regions, and elucidated their functional consequences on epigenome, transcriptome, and complex traits in pigs.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"188"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Refining the genetic structure and admixture history of Hmong-Mien populations.","authors":"Meiqing Yang, Huangzhen Huang, Han Zhang, Wen Wan, Kongyang Zhu, Rui Wang, Jinxi Li, Lu Chen, Jiang Huang, Chuan-Chao Wang","doi":"10.1186/s12915-025-02287-8","DOIUrl":"10.1186/s12915-025-02287-8","url":null,"abstract":"<p><strong>Background: </strong>Recent studies have shed light on the unique linguistic and genetic characteristics of Hmong-Mien speakers. However, the underlying genetic structure and admixture events that shape their genetic diversity remain inadequately elucidated.</p><p><strong>Results: </strong>Here, we co-analyzed newly generated genome-wide data from 164 individuals in Guizhou Province with published data from geographically proximate HM speakers using both allele frequency-based and haplotype-based methods. We unveiled fine-scale genetic substructure within HM speakers in southwest China, emphasizing distinct genetic differentiation between the Miao and Yao branches. Notably, Guangxi GaoHuaHua individuals showed close affiliation with the Yao branch, indicating a divergence time predating approximately 500 years ago. Besides, southwestern HM speakers exhibited an admixture pattern of indigenous Hmong and BaikuYao-like ancestry with minor contributions from neighboring populations like Tai-Kadai and Sino-Tibetan speakers in recent history. We finally identified the dominant paternal and diverse maternal lineages of HM speakers, implying a rich genetic tapestry and intricate historical migrations.</p><p><strong>Conclusions: </strong>Our study provided new insights into the genetic formation and admixture events that significantly shaped the genomic diversity of present-day HM speakers in southwest China.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"192"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12217280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GraphGIM: rethinking molecular graph contrastive learning via geometry image modeling.","authors":"Chaoyi Li, Hongxin Xiang, Wenjie Du, Tengfei Ma, Haowen Chen, Xiangxiang Zeng, Lei Xu","doi":"10.1186/s12915-025-02249-0","DOIUrl":"10.1186/s12915-025-02249-0","url":null,"abstract":"<p><strong>Background: </strong>Learning molecular representations is crucial for accurate drug discovery. Using graphs to represent molecules is a popular solution, and many researchers have used contrastive learning to improve the generalization of molecular graph representations.</p><p><strong>Results: </strong>In this work, we revisit existing graph-based contrastive methods and find that these methods have limited diversity in the constructed sample pairs, resulting in insufficient performance gains. To alleviate the above challenge, we propose a novel molecular graph contrastive learning method via geometry image modeling, called GraphGIM, which enhances the diversity between sample pairs. GraphGIM is pre-trained on 2 million 2D graphs and multi-view 3D geometry images through contrastive learning. Furthermore, we find that as the convolutional layers process the image becomes deeper, the information of feature maps gradually changes from global molecular-level information (molecular scaffolds) to local atomic-level information (molecular atoms and functional groups), which provides chemical information at different scales. Therefore, we propose two variants of GraphGIM, called GraphGIM-M and GraphGIM-P, which fuse feature maps of different scales in the image using a weighted strategy and a prompt-based strategy, respectively.</p><p><strong>Conclusions: </strong>Extensive experiments show that GraphGIM and its two variants outperform state-of-the-art graph contrastive learning methods on eight molecular property prediction benchmarks from MoleculeNet and achieve competitive results with state-of-the-art methods. The code is available at https://github.com/cyli029/GraphGIM .</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"189"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12219247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The demic expansion of Yangshao culture inferred from ancient human genomes.","authors":"Lei Sun, Hao Ma, Rui Wang, Zhijiang Wu, Limin Qiu, Haodong Chen, Chuan-Chao Wang","doi":"10.1186/s12915-025-02286-9","DOIUrl":"10.1186/s12915-025-02286-9","url":null,"abstract":"<p><strong>Background: </strong>Originating from the middle Yellow River, Yangshao culture is one of the most influential archaeological cultures in Neolithic China. It has long been debated whether there was a genetic substructure between the core Yangshao sites and those representing regional variants of the Yangshao culture, such as the Qinwangzhai culture. The excavated human remains from the burials at the Zhanmatun site, which belonged to the Qinwangzhai culture, present ideal material for inferring the population dynamics accompanying the cultural expansion.</p><p><strong>Results: </strong>In this study, we analyzed genome-wide data from 12 human remains obtained from the Zhanmatun site. The results indicated that Zhanmatun individuals were genetically homogeneous with all published Yangshao culture-related individuals from the core region of Yangshao and its periphery as well as Late Dawenkou culture-related Xixiahou people in the east, with no tracts of genetic influence from Neolithic Southern East Asian in the south.</p><p><strong>Conclusions: </strong>Our findings support a demic diffusion model for Yangshao culture expansion, where human migration, rather than mere cultural diffusion, played a dominant role in spreading Yangshao-related ancestry across northern China.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"186"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12218936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ophiocordyceps sinensis-induced changes in Thitarodes xiaojinensis: from intestinal barrier destruction, microbiome dysbiosis to immune responses at the molecular level.","authors":"Xiu-Wen Bao, Qing-He Wang, Ting Li, Yong Li, Zhi-Ying Bian, Si-Jing Liu, Li-Ying He, Shu-Qi Niu, Jin-Lin Guo","doi":"10.1186/s12915-025-02277-w","DOIUrl":"10.1186/s12915-025-02277-w","url":null,"abstract":"<p><strong>Background: </strong>The entomopathogenic fungus (EPF) Ophiocordyceps sinensis has a long-term coexistence with its host insect, Thitarodes xiaojinensis, making it a unique model for host-pathogen interactions. Hemolymph, a critical component in insects, plays an essential role in maintaining both nutritional and immune homeostasis. However, the mechanism of the host's immune response remains unclear when O. sinensis proliferates in the hemolymph.</p><p><strong>Results: </strong>O. sinensis caused damage to the insect's intestinal barrier, facilitating the translocation of gut bacteria into the hemocoel. Subsequently, the presence of O. sinensis and opportunistic pathogenic bacteria from the gut disrupted the homeostasis of the hemolymph microbiota, resulting in an increase in bacterial diversity. This disruption triggered a series of physiological responses in the host, including elevated levels of endocrine hormones specifically 20-hydroxyecdysone (20E) and juvenile hormone 3 (JH3). Additionally, there was an enhancement of antioxidant capacity, as indicated by increased total antioxidant capacity and glutathione S-transferase activity, along with the production of antimicrobial peptides (AMPs) as part of the immune defense. Notably, the rise in 20E levels during O. sinensis infection might have significantly contributed to the increased production of AMPs.</p><p><strong>Conclusions: </strong>O. sinensis infection significantly alters T. xiaojinensis physiology. Humoral immunity in infected hosts is primarily in response to hemolymph microbial homeostasis due to intestinal translocation. Among them, 20E upregulates AMP-related genes, suggesting a key immune strategy for managing microbial imbalances while tolerating fungal pathogens.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"183"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AmpHGT: expanding prediction of antimicrobial activity in peptides containing non-canonical amino acids using multi-view constrained heterogeneous graph transformer.","authors":"Yongcheng He, Xu Song, Hongping Wan, Xinghong Zhao","doi":"10.1186/s12915-025-02253-4","DOIUrl":"10.1186/s12915-025-02253-4","url":null,"abstract":"<p><strong>Background: </strong>Antimicrobial peptide (AMP) prediction has been extensively studied in recent years. However, many existing models do not fully leverage the intrinsic chemical structures of AMPs, such as atomic composition and sidechain group characteristics. Instead, these models often focus on letter composition, positional encodings, and pre-defined chemical-physical descriptors. The incorporation of non-canonical amino acids, which enhance peptide stability and reduce toxicity, is getting more attention in peptide design. Despite this, they are overlooked in predictive studies, as traditional deciphering methods and single-letter representation systems are inadequate for this task. Even though some efforts have been made to expand current alphabets, these approaches remain insufficient, impeding the development of novel AMPs.</p><p><strong>Results: </strong>A novel deep learning model, termed AmpHGT, was developed based on heterogeneous graphs' representation of peptides. AmpHGT demonstrates competitive performance against current methods on canonical amino acid benchmarks. Notably, AmpHGT is capable of efficiently classifying antimicrobial peptides with non-canonical amino acids, addressing the limitations of traditional feature extraction methods. In addition, this model is adaptable to handling different conformations, sidechains, and backbones (e.g., α, β, γ), demonstrating its potential to enhance the screening and discovery of AMPs containing non-canonical amino acids.</p><p><strong>Conclusions: </strong>Our study suggests that AmpHGT is reliable for antimicrobial peptide classification task. It may serve as an efficient primary filter for evaluating thousands of mined peptides and provides a good foundation for future studies aimed at producing peptide antibiotics containing non-canonical amino acids.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"184"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12217533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astaxanthin prevents postovulatory oocyte aging by targeting TNFR2 and inhibiting the TNF signaling pathway.","authors":"Xin Wen, Zhe Han, Qi Yang, Ke-Song Shi, Dui Sun, Xiao-Jie Zhang, Cheng-Guang Liang","doi":"10.1186/s12915-025-02292-x","DOIUrl":"10.1186/s12915-025-02292-x","url":null,"abstract":"<p><strong>Background: </strong>MII oocytes undergo time-dependent aging after ovulation, which is closely associated with impaired fertilization potential, poor embryo quality, and an increased risk of miscarriage. The apoptosis of cumulus cells and their secretion of TNF-α are identified as the primary contributors to postovulatory oocyte aging.</p><p><strong>Results: </strong>In this study, we demonstrated that astaxanthin supplementation in culture medium effectively prevents postovulatory oocyte aging and extends oocyte lifespan in vitro. Importantly, this protective effect does not operate through the inhibition of cumulus cell apoptosis or TNF-α release. Notably, astaxanthin selectively binds to TNFR2 in oocytes, thereby preventing TNFR2 from interacting with TNF-α and inhibiting the activation of the TNF signaling pathway within oocytes. Furthermore, oocytes cultured with astaxanthin exhibit enhanced potential for early embryonic development and significantly increased IVF-ET litter size compared to controls.</p><p><strong>Conclusions: </strong>Our findings, based on a mouse model, provide valuable insights into the potential clinical application of astaxanthin in mitigating post-ovulatory oocyte aging.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"176"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}