Biology subjects

Xu, L.

Publications and source records attributed to Xu, L..

At least 91 records · Page 5Linked to original sources

bioRxiv2026

Dysregulation of xenobiotic metabolism and mitochondrial dysfunction exacerbate acetaminophen-induced hepatotoxicity in human antigen R-deficient male mice

Acetaminophen (APAP) overdose is a leading cause of acute liver failure worldwide. The RNA-binding protein Human antigen R (HuR) is a multifunctional post-transcriptional regulator that plays a pivotal role in cellular stress responses, including those triggered by APAP toxicity. This study investigated the mechanisms by which HuR protects against APAP-induced hepatotoxicity in male mice. Hepatocyte-specific HuR-deficient (HuRHep-/-) male mice on a C57BL/6N background and wild-type (WT) littermates were treated with 200 mg/kg APAP, and liver tissues were collected at 2, 6, and 24 hours post-treatment. APAP administration increased hepatic HuR mRNA expression and induced HuR cleavage and the formation of a higher-molecular weight HuR-immunoreactive band, with the latter two correlating with injury severity. Compared with WT controls, HuRHep-/- mice exhibited markedly increased susceptibility to hepatotoxicity at both 2 and 6 hours. Metabolite profiling revealed altered APAP metabolism and reduced glutathione S-transferase (Gst) expression in HuRHep-/- livers, consistent with impaired APAP detoxification and increased APAP-protein adduct formation. Fourier-transform infrared (FTIR) spectroscopy further identified early biochemical differences between WT and HuRHep-/- livers as early as 2 hours after APAP exposure. Additionally, HuR deficiency resulted in pronounced mitochondrial structural abnormalities and dysfunction at 2 and 6 hours, accompanied by reduced expression of the mitochondrial fission and fusion proteins Drp1 and Mfn2, increased mitochondrial protein release, and enhanced hepatocyte death. Although pro-inflammatory cytokine levels were elevated in HuRHep-/- mice relative to WT controls at 24 hours, hepatocyte proliferation was similarly blunted in both genotypes, consistent with severe liver injury and delayed recovery. Collectively, these findings identify hepatocyte HuR as a critical regulator of xenobiotic metabolism and mitochondrial integrity and establish its essential role in early protection against APAP-induced hepatotoxicity in male mice.

pharmacology and toxicology↗

bioRxiv2026

Prime-InDel version 1: A web tool providing InDel markers for targeted regions narrowing

While high-density SNP genotyping enables genome-wide assays in rice (Oryza sativa L.) and other crops, PCR-based markers--particularly those derived from insertion-deletion (InDel) variations--remain crucial for fine-mapping. Currently, readily available primer information for high-density InDel rice markers is still limited. We present the first version of PrimeInDel (https://rfgb.rmbreeding.cn/search/variation/primeIndel), an online tool integrating three sets of InDel markers: an 8K-set and a 316K-set from the 3K Rice Genomes (3K-RG) project, and a 22K-set compiled from published literatures. In user cases, primers from PrimeInDel proved highly effective, narrowing a cold-tolerance QTL (qSR2) from 2.7 Mb to 200 kb and a heading-date QTL (qDeh1.1) from 239.5 kb to 83.6 kb. Our work provides the community with a robust, PCR-based InDel primer, accessible via an online data set, which will facilitate germplasm genotyping and gene identification in rice breeding.

plant biology↗

bioRxiv2026

Spatially resolved transcriptome-metabolome integration reveals region-specific glial lipid dysregulation associated with Alzheimer's pathology

Glial cells maintain the brains lipid and energy balance, and their breakdown is increasingly recognized as a causal contributor to Alzheimers disease (AD). While this concept is established, no approach has directly shown how glial homeostatic failure manifests across brain regions and microenvironments or how it links local pathology, such as plaques, to global metabolic imbalance. To address this gap, we developed iMIST, an integrated platform that combines MALDI-based metabolite imaging, histology, and spatial transcriptomics within a single tissue section to align molecular and anatomical information. Using a mouse model of late-onset AD that recapitulates both amyloid deposition and metabolic vulnerability, iMIST revealed that glial lipid dysregulation is widespread but spatially specialized. In gray matter, plaque-associated microglia were associated with upregulated glycerophospholipid-remodeling in cortico-thalamic areas indicating metabolic stress around local pathology. In contrast, white matter tracts rich in lipid-producing oligodendrocytes show plaque-independent deficits in galactosylceramide metabolism reflecting their high myelin demand. Both processes intensify with age, transforming adaptive glial responses into persistent metabolic dysfunction. Together, these findings demonstrate the spatial interplay between global glial metabolic imbalance and local microenvironmental stressors associated with AD pathology. By integrating transcriptomic and metabolomic information in situ, iMIST provides a framework for uncovering how regional glial vulnerability shapes the pathogenesis of neurodegenerative diseases.

neuroscience↗

bioRxiv2026

eTRex Reveals Oncogenic Transcriptional Regulatory Programs Across Human Cancers

Transcriptional regulators (TRs) are essential proteins that regulate gene transcription, and their dysregulation defines the oncogenic transcriptional regulatory programs that drive tumor-specific gene expression. Existing pan-cancer resources summarize these programs by aggregating signals across individual datasets, neglecting the context-specific features that capture the diversity of transcriptional regulation underlying cancer heterogeneity. By developing a variational Bayesian hierarchical model named eTRex (epigenomics-based Transcriptional Regulator explorer) and applying it to 4,819 cancer-related ATAC-seq datasets, we provide a comprehensive pan-cancer atlas of functional TR profiles that preserve the context-specific features of each dataset. This study reveals both common regulators across diverse malignancies and those with highly specific roles. We extensively validated these findings using independent CRISPR/Cas9 screening, mutation, and transcriptomic datasets. Collectively, this pan-cancer atlas of functional TR profiles represents a comprehensive, biologically interpretable resource for uncovering transcriptional regulatory programs, identifying biomarkers, prioritizing therapeutic targets in oncology, and is freely accessible through an interactive web portal.

bioinformatics↗

bioRxiv2026

Establishing the molecular basis for MDA5 mutation-linked autoimmunity

Melanoma differentiation-associated protein 5 (MDA5), a member of the RIG-I-like receptor family, is a cytoplasmic sensor essential for innate antiviral immunity. MDA5 distinguishes viral RNA from host RNA in part through its ATP hydrolysis activity, which promotes filament turnover on shorter endogenous dsRNAs. Here, we show that the gain-of-function T331I disease-linked mutation within the ATP binding pocket disrupts this balance, resulting in constitutive interferon signaling. Through a combination of cryo-electron microscopy (cryoEM), biochemical assays, and cellular analyses, we reveal the extensive network of interactions that precisely position ATP for catalysis in the wild-type MDA5 ATP binding pocket, and also demonstrate that the T331I mutation impairs ATPase activity, thereby stabilizing MDA5-dsRNA complexes and leading to aberrant immune activation. These findings elucidate how MDA5 ATPase activity regulates antiviral specificity and prevents autoimmunity by controlling filament stability and downstream signaling, offering a mechanistic molecular explanation for disease pathogenesis.

biochemistry↗

bioRxiv2026

L-cysteine inhibited the growth of Vibrio parahaemolyticus via increasing the ROS level

The emergence of multidrug-resistant Vibrio parahaemolyticus poses a severe threat to mariculture sustainability, highlighting the urgent need for eco-friendly antimicrobial agents. In this study, we demonstrated that L-Cysteine (L-Cys) functions as an inhibitor of V. parahaemolyticus, with a minimum inhibitory concentration of 7.5 mM. Microscopic observation and viability assays revealed that L-Cys compromises bacterial membrane integrity, ultimately leading to cell death. Further investigation indicated that the antibacterial effect is primarily attributed to the intracellular production of hydrogen sulfide (H2S) generated by L-Cys metabolism. Transcriptomic and biochemical analyses showed that L-Cys induced metabolic reprogramming by suppressing fatty acid {beta}-oxidation, one-carbon metabolism, and antioxidant enzymes. This disruption of redox homeostasis results in accelerated accumulation of reactive oxygen species (ROS). In addition to its antibacterial effect, L-Cys also effectively reduced the virulence factor of bacterial motility. Finally, L-Cys demonstrated broad-spectrum antimicrobial activity against other pathogenic Vibrio species, including V. alginolyticus and V. anguillarum. Our findings suggest that L-Cys is a promising antimicrobial agent inducing ROS to mediate membrane disruption, with the advantages of cost-effectiveness and environmental safety for controlling vibriosis. ImportanceVibrio parahaemolyticus is a significant pathogen in aquaculture and a common cause of seafood-borne gastroenteritis worldwide. The increasing prevalence of antibiotic-resistant strains of this bacterium highlights the need for alternative control agents. This study shows that L-cysteine (L-Cys) inhibits the growth of V. parahaemolyticus. Our data indicate that L-Cys is metabolized to produce hydrogen sulfide, which contributes to the accumulation of ROS and disrupts bacterial membrane integrity. Additionally, L-Cys reduces bacterial motility and shows inhibitory effects against other Vibrio species. These findings suggest that L-Cys may represent a useful agent for managing Vibrio infections in aquaculture settings.

microbiology↗

bioRxiv2026

3D reconstruction of spatial transcriptomics with spatial pattern enhanced graph convolutional neural network

Spatially resolved transcriptomics (SRT) is a promising new technology that enables simultaneous analysis of gene expression and spatial information for biomedical research. However, the existing statistical and deep learning algorithms used for analyzing SRT data rely solely on two-dimensional (2D) spatial coordinates, which limits their ability to accurately identify spatial domains, spatially variable genes, cell-to-cell communications, and developmental trajectories in a three-dimensional (3D) spatial manner. To address these limitations, we introduced Spa3D, which utilized the anti-leakage Fourier transform and graph convolutional neural network model to reconstruct 3D-based spatial structures from multiple 2D SRT slices. We demonstrate that Spa3D is appliable to analyze data from various SRT technology platforms and outperforms state-of-art methods by: (I) improving spatial domain identification through 3D reconstruction, (II) elucidating cell-cell communication landscape in the 3D cellular organization, (III) modeling of organ-level tempo-spatial development patterns in a 3D fashion, and (IV) annotating 3D spatial trajectory that are not captured by 2D spatial coordinates. Key pointsO_LIMost existing spatial omics analysis methods rely on 2D data, limiting their ability to capture full spatial and developmental tissue complexity C_LIO_LISpa3D incorporates physical z-axis distances, enabling accurate 3D modeling even when adjacent slices vary in tissue structure and composition C_LIO_LISpa3D reconstructs true 3D spatial structures from 2D SRT slices using graph convolutional networks and anti-leakage Fourier transforms C_LIO_LISpa3D enhances spatial domain detection, revealing detailed cell-cell communication and organ-level development patterns across multiple spatial omics platforms C_LIO_LISpa3D enables novel biological discoveries by revealing spatial features and trajectories not detectable using traditional 2D transcriptomic analysis approaches C_LI

bioinformatics↗

bioRxiv2026

Development of Integrin α5β1-targeted PET/NIR imaging probes for glioblastoma intraoperative navigation and intracavity targeted radionuclide therapy

Incomplete extent of tumor resection is the major factor of glioblastoma recurrence, leading to its poor prognosis. Developing therapies that enable the minimal tumor cell remnant during surgical resection is a major challenge to combat this aggressive cancer. This study develops a glioblastoma integrin 5{beta}1-selective peptide binder through series strategy screening and labeling it with 68Ga, indocyanine green (ICG), or 177Lu for efficacious multimodal treatment. This strategy combines positron emission tomography (PET) imaging for preoperative diagnosis, intraoperative NIR-II fluorescence-guided surgery for maximal tumor resection, and followed by intracavity targeted radionuclide therapy for elimination of residual tumor cells. We identified GR, with five arginine mutation, exhibiting superior integrin 5{beta}1 binding affinity and brain penetration. [68Ga]GR demonstrated substantial tumor uptake and prolonged retention time in both mouse models and tissues from glioblastoma patients. The guidance of ICG-GR achieved accurately intraoperative tumor imaging and maximal tumor resection in orthotopic mouse glioblastoma models. Notably, combining intracavity administration of [177Lu]GR following ICG-GR guiding resection markedly inhibited tumor growth and reduced possibility of tumor recurrence compared with surgery alone (unguided or ICG-GR-guided) or unguided surgery followed by [177Lu]GR. Therefore, we have reported the integrin 5{beta}1-targeted radionuclide and optical agents for maximal elimination of tumor cells during surgical resection in glioblastoma patients. HIGHLIGHTSO_LIGR is a glioblastoma-specific peptide with both favorable binding affinity superior brain penetration. C_LIO_LIICG-GR is a glioblastoma-targeted NIR probe enabling maximal surgical resection. C_LIO_LIICG-GR-guided surgery with [177Lu]GR-based adjuvant therapy allows robust elimination of tumor cells. C_LI

cancer biology↗

bioRxiv2025

Vitreous Inflammation as an Early Indicator of Retinal Ganglion Cell Loss Following Acute Optic Nerve Injury in Mice

Retinal ganglion cell (RGC) degeneration in optic neuropathies is often preceded by neuroinflammatory changes, yet the earliest in vivo indicators of this process remain poorly defined. Here, we identified vitreous hyperreflective foci (VHRFs) by visible-light optical coherence tomography (vis-OCT) as an early inflammatory signature of RGC injury. Longitudinal vis-OCT imaging after optic nerve crush (ONC) revealed that VHRFs emerged as early as 6 hours post-injury and peaked before the significant RGC loss. Confocal analysis showed that these VHRFs corresponded to activated amoeboid microglia undergoing vertical migration from the outer to inner retina and horizontal movement toward the optic nerve head area. Similar amoeboid microglia were also observed in the anterior segment, suggesting a global ocular inflammatory response to the ONC injury. RNAscope in situ hybridization further demonstrated elevated IL-1{beta} expression in vitreous amoeboid microglia. Moreover, pharmacological blockade of IL-1 signaling with an IL-1 receptor antagonist significantly reduced VHRFs, suppressed microglial migration, and delayed RGC loss. Taken together, our findings identify VHRFs as a previously unrecognized early danger signal for RGC degeneration and highlight IL-1-mediated inflammation as a tractable early therapeutic target for preventing RGC degeneration and vision loss. Graphical Overview O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=88 SRC="FIGDIR/small/694725v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@1598c4aorg.highwire.dtl.DTLVardef@9637borg.highwire.dtl.DTLVardef@623bf4org.highwire.dtl.DTLVardef@14e21ce_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2025

Human trunk embryoids with patterned anterior-posterior and dorsal-ventral body axes: utility for understanding human development and disease

Human embryoid models enable mechanistic studies of development and disease. We generated trunk embryoids from human pluripotent stem cells that recapitulate posterior trunk formation at Carnegie stage (CS) 8-10, with patterned anterior-posterior (A-P) and dorsal-ventral (D-V) axes. These self-organizing structures comprise a ventral notochord, dorsal neural tube, floor plate and bilateral somites. Genetic and chemical perturbations of SHH signaling confirmed the notochords central role in D-V patterning. Moreover, VANGL1/2 loss-of-function mutations recapitulated mouse phenotypes, including axial truncation and somite segmentation failure. This model enables detailed study of key developmental events that underlie posterior trunk formation and provides a promising platform for human disease modeling.

developmental biology↗

bioRxiv2025

AlphaFold 3-powered discovery of phage proteins that inhibit bacterial transcription

Phages are the most abundant biological entities on Earth and play central roles in bacterial evolution and the emergence of new pathogens. Many phages encode proteins that specifically inhibit host RNA polymerase activity, thereby sabotaging and, in some cases, hijacking the host transcription machinery to serve their needs. Identification and characterization of these transcription inhibitors not only provide insights into the logic of transcription regulation but also inspire the design of antibiotics targeting bacterial transcription. Traditional methods for identifying new phage proteins that inhibit bacterial transcription are labor-intensive and require access to live phages. To overcome these limitations, we developed a highly efficient pipeline for AlphaFold 3-guided discovery of phage proteins that inhibit bacterial transcription. Using this pipeline, three phage proteins were identified and characterized. Structural and biochemical analyses demonstrated that these phage proteins bind to distinct sites on RNA polymerase and inhibit transcription via unprecedented mechanisms. This study showcases the power of AlphaFold 3 in discovering novel binders of large protein complexes, and the pipeline developed here could be readily adapted to screen modulators of other large targets, such as the ribosome, proteasome, and CRISPR-Cas systems.

molecular biology↗

bioRxiv2025

Comprehensive perturbation of transcription factors in human cardiomyocytes reveals the regulatory architecture of congenital heart disease

Transcription factors (TFs), including DNA binding proteins and epigenetic co-regulators, control the timing of gene programs during lineage commitment1. However, systematically defining the dynamic activities of the human genomes nearly 2000 TFs during development remains challenging2,3. Here, we use Perturb-Seq to map the transcriptional impact of nearly all human TFs and a subset of enhancers during cardiomyocyte differentiation. Our results suggest that developmental regulatory networks are distributed across highly connected hub TFs4-6 that are dynamic across lineage and time, rather than organizing into top-down hierarchies directed by "master regulators". We also identify distinct TF ensembles that regulate sequential decision points during cardiac cell-fate specification by coordinating lineage-specific activation with alternate lineage repression. Separately, analysis of TF-TF cooperativity uncovers a dynamic interaction between MEF2 family TFs7 and members of the Polycomb Repressive complex 18-10 to execute alternative fate repression. Building on these regulatory interactions, we construct a deep learning transformer model to accurately predict perturbed TFs driving altered regulatory networks in patient-derived transcriptomes. Together, our results define the regulatory network architecture of human lineage specification and provide a platform for predicting TF function and interpreting disease mechanisms.

genomics↗

bioRxiv2025

White-Matter BOLD Mediates Time-Varying Cortico-Cortical Functional Connectivity

Functional connectivity (FC) measurements in the brain using BOLD fMRI have largely focused on correlations between gray-matter (GM) BOLD signals, ignoring the possible relevance of white-matter (WM) in delineating neural networks. We first employed a tract-informed mediation framework to test whether WM pathways contribute indirect, bundle-specific effects to cortico-cortical coupling. Using resting-state fMRI data from the Human Connectome Project, we quantified pathway-level mediation effects across GM-WM-GM units and found that WM BOLD signals significantly mediated GM-GM associations, with clear tract-dependent heterogeneity. Building upon this, we examined how dynamic features of WM BOLD signals relate to time-varying intra-cortical FC. We found that temporal variability of WM signals, rather than their mean amplitudes, more closely tracked fluctuations in GM-GM dynamic connectivity, with correlations reaching approximately 0.4 across specific tracts. Together, these results indicate that WM BOLD signals are related to how cortical regions interact, underscoring their integral role in large-scale brain network organization.

neuroscience↗

bioRxiv2025

Antibody feedback establishes an affinity brake in the germinal center

Recent advances in mRNA vaccine technology have opened the door to novel types of antigen display, but little is yet known as to how B cells recognize and respond to these formats. By delivering an mRNA-LNP encoded membrane-bound immunogen displaying three conserved HIV-1 Envelope (Env) epitopes to knock-in mouse models with B cell receptors (BCRs) of defined affinities, we investigated how epitope-specific competition shapes germinal center (GC) responses. Co-activation of B cells targeting different epitopes did not alter GC kinetics observed in individual activations, but a striking inverse correlation was observed between BCR affinity and GC residence time in either scenario: high-affinity B cells exhibited shorter persistence in GCs, while those with lower affinity to the antigen were maintained. Furthermore, B cells were able to engage in GC reactions at equivalent rates in the presence or absence of clonal lineages binding the same epitope with similar affinities, while higher-affinity clones suppressed lower-affinity counterparts targeting the same epitope. Spatial transcriptomics revealed plasma-like cells within and adjacent to the GC which, together with the detection of early IgG in draining lymph nodes, suggests that local antibody production from these cells may contribute to feedback-driven kinetics. These findings indicate that a self-modulated local antibody feedback loop may act as a "brake" on epitope-specific recognition--dampening further affinity enhancement for high-affinity B cells and facilitating epitope spreading by redirecting the response toward alternative epitopes.

immunology↗

bioRxiv2025

The phylogenetic Janzen-Connell effect can explain multiple macroecological and macroevolutionary patterns

The classical Janzen-Connell (J-C) hypothesis states that species-specific natural enemies induce local-density dependence which explains high diversity observed in tropical tree communities. Recent studies have extended the hypothesis to include the fact that these natural enemies often attack phylogenetically related species as well, which reduces diversity and hence the explanatory power of the hypothesis. However, these studies consider ecological time scales at which the phylogenetic relatedness between species is constant, and thus ignore that at evolutionary time scales the population dynamics change the phylogeny. We use a spatially explicit eco-evolutionary model of the interplay between the dynamics of the phylogeny and the species abundances to study the predictions for common macroevolutionary and macroecological patterns. We confirm that hyperdiversity can be maintained by the J-C effect but the phylogenetic relatedness effect weakens the rarity advantage, reducing diversity. Incorporating protracted speciation further improves the result. Our model predicts a triphasic species-area relationship at much shorter time scales than in neutral scenarios. The species-abundance distribution can have one or two modes depending on the dispersal distance. Phylogenetic trees show diversification slowdowns and imbalance, consistent with empirical patterns. We study a new pattern of phylogenetic relatedness through space and find that small dispersal distance causes clusters of species with large phylogenetic distance to the community while large dispersal distance makes species distribute uniformly. As an illustration of how our models predictions can be compared to empirical data we study macroecological and phylogenetic patterns of the Barro Colorado Island (BCI) tree community. We conclude that the spatially explicit eco-evolutionary phylogenetic J-C effect can explain commonly observed macroevolutionary and macroecological patterns, providing an alternative way, while the traditional methods are prone, to demonstrate the role of J-C effect on species community assembly.

evolutionary biology↗

bioRxiv2025

Nurture over nature in new Micromonospora spp. strains metabolism: multi-omics analyses reveal fermentation conditions as the dominant driver over phylogeny

The genus Micromonospora, a key member of the actinomycetes, has demonstrated considerable potential for natural product biosynthesis. In this study, we isolated 15 Micromonospora spp. strains from desert soil and marine sediment samples, eight of which represent four novel species. To explore the biosynthetic capacity of this genus, we performed an integrated analysis of Micromonospora reference genomes. Pan-genomic analysis further unveiled the core biosynthetic characteristics of the genus responsible for producing terpenes and polyketides. Further multi-omics investigation, combining genomic and metabolomic data, uncovered a positive correlation between phylogenetic relationships and biosynthetic potential, alongside a decoupling of metabolic profiles. Notably, metabolomic findings emphasized the dominant influence of culture conditions on the expression of biosynthetic capabilities. Overall, our study provides a comprehensive elucidation of the biosynthetic potential of the genus Micromonospora and highlights the value of investigating novel strains and applying diverse cultivation strategies in natural product discovery. ImportanceOur study provides a comprehensive genomic and metabolomic elucidation of the significant biosynthetic potential within the genus Micromonospora. It reveals a core biosynthetic capacity for terpenes and polyketides that is phylogenetically linked, whereas the resulting natural product repertoire is subject to strong modulation by cultivation conditions. These findings underscore the critical importance of exploring novel species and employing diverse cultivation strategies to unlock the full potential of microbial resources for natural product discovery.

microbiology↗

bioRxiv2025

Facilitation-competition tradeoffs structure microbial niches and nitrogen cycling

The marine nitrogen cycle is regulated by ecological interactions among diverse microbial populations, especially in oxygen minimum zones where populations carrying out anaerobic metabolisms, mainly denitrification and anammox, drive fixed nitrogen loss. While competition for limiting resources is well studied, the combined effects of competition and facilitation, where a "feeder" population supplies a required resource to a "recipient", remain poorly understood. Here we develop a trait-based consumer-resource framework to test how recipient populations reshape the ecological niches of their feeders and competitors. Invasion analysis shows that recipients expand either their feeders or the feeders competitors niche, depending on the populations relative competitive abilities on limiting resources. In terms of biogeochemistry, ecological outcomes result in diverse N-loss pathways; specifically, when growth is limited by both organic matter and nitrate, we observe increased nitrous oxide production. Additionally, the model suggests that anammox bacteria occupy a wider range of organic matter and nitrate supply regimes than denitrifying populations, consistent with their more frequent detection across diverse marine environments. The results link microbial interaction networks to biogeochemical fluxes relevant at global scales, and extend ecological theory to multi-resource systems with nested competitive and facilitative interactions.

microbiology↗

bioRxiv2025

The emerging contaminant Cl-PFESA/F-53B is toxic to meiotic cell division and reproduction in Arabidopsis thaliana

The emerging contaminant Cl-PFESA/F-53B damages vegetative development in plants and has been evidenced to be toxic to both mitotic and meiotic cells in animals. We have recently reported that F-53B induces nuclei unviability in meristematic cells leading to disrupted root development in Arabidopsis (Arabidopsis thaliana). However, the toxicity of F-53B to reproductive system in plants remains unelucidated. In this study, by using cytogenetic and microscopic approaches, we analyzed embryo and anther development and multiple meiosis processes in Arabidopsis exposed to 50 or 100 M F-53B. We showed that F-53B disrupts embryo development which results in reduced seed setting in Arabidopsis. Histochemical staining of anthers and a live-imaging assay using a reporter line that expresses GFP-tagged Aborted Microspores (AMS), a key regulator of the tapetum, demonstrated that F-53B impairs anther development. Moreover, we showed that F-53B interferes with chromosome segregation and/or distribution and alters microtubule organization during male meiosis. Quantification of the chiasmata and immunolocalization of the Human Enhancer of Invasion 10 (HEI10) protein on diakinesis chromosomes suggested that F-53B reduces crossover rate. Furthermore, F-53B reduced the number of DNA Meiotic Recombinase 1 (DMC1) protein foci on zygotene chromosomes in Arabidopsis wild-type Columbia-0 (Col-0), and it partially promoted meiotic chromosome integrity in Arabidopsis depleted with Ataxia Telangiectasia Mutated (ATM), a central regulator of DNA double-strand break (DSB) repair, which suggested that F-53B reduces meiotic DSB formation. Taken together, our study reveals the toxicity of F-53B to meiotic cells and reproduction in Arabidopsis, which highlights its potential threats to agricultural safety and ecological diversity. HighlightO_LIF-53B impairs embryo and anther development in Arabidopsis. C_LIO_LIF-53B interferes with chromosome segregation and distribution during male meiosis. C_LIO_LIF-53B interferes with meiotic microtubule organization. C_LIO_LIF-53B reduces meiotic crossover formation. C_LIO_LIF-53B reduces DNA double-strand breaks in meiocytes. C_LI

plant biology↗