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At least 19 recordsLinked to original sources
PubMed2026

Bioactivity and developmental toxicity of Raphanus raphanistrum: integrating phytochemistry, in vitro assays, and zebrafish model.

Raphanus raphanistrum L. (wild radish), a member of the Brassicaceae family, is an edible herb widely utilized in traditional medicine for the treatment of various ailments. This study aimed to evaluate the chemical composition, antioxidant capacity, enzyme inhibitory potential, and cytotoxic activity of extracts derived from its aerial parts. Among the tested extracts, the 70% ethanol extract contained the highest total phenolic content. A total of 38 compounds, mainly phenolic acids and flavonoids, were identified by HPLC-ESI-MS/MS analysis. The aqueous extract contained the highest levels of individual phenolic compounds, particularly ferulic acid and p-coumaric acid. The 70% ethanol extract showed the strongest antioxidant activity in all assays. The ethyl acetate extract exhibited the highest acetylcholinesterase and α-amylase inhibitory activities. Cytotoxicity assays revealed that the 70% ethanol extract was active against A549 lung cancer cells with an IC50 value of 56.77 µg mL-1 and a selectivity index of 1.6. In vivo zebrafish developmental toxicity assays demonstrated dose-dependent embryotoxic effects. Early exposure (0 hpf) caused increased mortality, reduced hatching, and morphological abnormalities, such as axial curvature and pericardial edema, whereas exposure at 72 hpf showed markedly reduced sensitivity. Overall, the findings suggest that R. raphanistrum is a promising natural source of bioactive compounds that could be used in the nutraceutical, pharmaceutical and cosmeceutical industries.

Journal Article↗
PubMed2025

Uncovering parental exposure risks of TCPP: Impaired development and metabolic homeostasis in zebrafish offspring.

As brominated flame retardants are phased out, tris (1‑chloro-2-propyl) phosphate (TCPP), a phosphorus-based flame retardant, has emerged as a prominent detectable flame retardant in the environment. However, TCPP has been found to exhibit endocrine-disrupting effects on organisms, raising significant safety concerns. In our study, we utilized the zebrafish model to explore the toxic effects of parental TCPP exposure on offspring and uncover its regulatory mechanisms through metabolomics analysis. Moreover, the impact on the nervous system and lipid metabolism was examined through behavioral analysis and specific staining. Our findings demonstrated that both embryonic and parental TCPP exposure induced developmental disorders in larvae, along with decreased locomotor activity and disordered lipid metabolism homeostasis. Parental exposure to TCPP, exhibiting stronger developmental toxicity than direct embryonic exposure, notably led to reductions in crucial energy substrates such as amino acids and carbohydrates. Meanwhile, embryonic TCPP exposure primarily affected the endogenous lipid-related metabolites including phospholipids, lipid-soluble vitamins, steroids and fatty acids, promoting lipid accumulation in larval liver and subcutaneous tissue. What's more, continuously parental and embryonic exposure showed the most pronounced effects on zebrafish development and metabolic regulation. Our study highlights the risk posed by parental exposure to TCPP on offspring zebrafish, underscoring the need for comprehensive consideration of the impact from parental exposure in pollutants regulation.

Animals↗
PubMed2025

Toxicological Assessment of Melamine-Functionalized Graphene Oxide and Carbon Nanotubes Using Zebrafish Models.

Graphene oxide (GO) and carbon nanotube (CNT)-based nanomaterials have attracted significant interest in various industrial and biomedical applications due to their unique physicochemical properties; however, concerns about their potential toxicity, especially when modified with additives like melamine (M), remain largely unresolved. This study investigates the toxicological effects and underlying mechanisms of graphene oxide-melamine (GO-M) and carbon nanotube-melamine (CNT-M) nanoparticles in zebrafish (Danio rerio) embryos and larvae. To this end, developmental toxicity, phenotypic and behavioral changes, as well as histopathological and immunofluorescence alterations, were evaluated following acute exposure to GO-M and CNT-M nanoparticles at concentrations of 5, 10, and 20 mg/L. Results showed that both nanoparticles delayed larval hatching, particularly at higher concentrations (10 and 20 mg/L). Malformations were observed at 20 mg/L in the GO-M group and at 10 and 20 mg/L in the CNT-M group. Additionally, significant changes in larval length and eye area were observed at all concentrations for both nanoparticles. Behavioral assessments revealed that CNT-M exposure at 10 and 20 mg/L significantly impaired head sensorimotor reflexes, while all concentrations affected tail reflexes. In contrast, GO-M exposure did not significantly alter sensorimotor responses. These findings suggest differential toxic mechanisms and neurobehavioral effects of GO-M and CNT-M nanoparticles during early zebrafish development.

Animals↗
PubMed2026

A review on the environmental distribution, toxic effects, bioaccumulation characteristics and risk assessment of short-chain chlorinated paraffins.

Chlorinated paraffins (CPs) are synthetic chemicals, widely used as flame retardants and plasticizers. As emerging contaminants, short chain chlorinated paraffins (SCCPs) have attracted tremendous attention due to their persistence, chronic toxicity, long-range transport potential and bioaccumulation potential. This review synthesizes global data on SCCPs' environmental occurrence, toxicological impacts, and bioaccumulation characteristics. SCCPs are ubiquitously detected in various environmental media, including water, sediment, air, soil, and biota. Ecotoxicological studies reveal that SCCPs have lethality, carcinogenicity, growth and developmental toxicities, organs toxicities and endocrine-disrupting effects across species, which pose risks to ecological systems and human health. In addition, the bioaccumulation effects of SCCPs in terrestrial and aquatic ecosystems were analyzed, and proposed the key factors affecting the bioaccumulation of SCCPs. Finally, the risk assessment of SCCPs contamination in the surface water and the soil was carried out, and all soil and most water bodies were found to be low risk. The present study could provide scientific basis and reference for environmental management of CPs products.

Paraffin↗
PubMed2026

Mechanisms of Hexavalent Chromium-Induced Reproductive Toxicity: A Focus on the Ovary and Placenta.

Hexavalent Chromium (Cr(VI)) is a Group A carcinogen, mutagen, and teratogen. Cr(VI) has been used by more than 50 industries, and its contamination of drinking water is widespread across the United States (U.S.). Epidemiological data of women who lived in Willits, California, U.S., indicate that environmental exposure to Cr(VI) adversely affects pregnancy outcomes and the health of their immediate offspring, resulting in a low birth rate, pregnancy loss, and spontaneous abortion, and their children (F1 offspring) experienced birth defects. However, the molecular mechanisms behind Cr(VI)-induced reproductive and developmental toxicity are poorly understood. Cr(VI) enters cells through anion transporters and is rapidly reduced to Cr(III) by endogenous antioxidants within the cell. Cr(III) forms adducts with DNA, which can block DNA replication and transcription; abnormal repair can lead to DNA double-strand breaks, mutations, micronucleus formation, chromosomal abnormalities, and increased genomic instability. Cr(VI) induces oxidative stress via the Fenton reaction, generating free radicals, and depleting antioxidants, thereby promoting apoptosis via p53-dependent and independent pathways, resulting in follicular atresia and accelerated reproductive aging. Antioxidant supplementation with resveratrol, vitamin C, and edaravone mitigates Cr(VI) toxicity in the ovary. Cr(VI) disrupts meiosis in metaphase II oocytes by causing DNA strand breaks, altering F-actin dynamics, disturbing microtubules, and leading to chromosome missegregation. Gestational exposure to Cr(VI) also disrupts placental function through multiple mechanisms by targeting trophoblast lineages. The current review focuses on genotoxicity, oxidative stress, and other mechanisms by which Cr(VI) disrupts the female reproductive and endocrine systems, with particular emphasis on the ovary and placenta.

Hexavalent chromium↗
PubMed1977

Genetically mediated induction of drug-metabolizing enzymes associated with congenital defects in the mouse.

Various polycyclic aromatic compounds induce certain monooxygenase activities, including aryl hydrocarbon (benzo[a]pyrene) hydroxylase (EC 1.14.14.2), and cytochrome P1-450 in the liver and many nonhepatic tissues of the mouse. This induction process is controlled by the Ah locus. Genetic differences that have been shown in the past to be associated with the Ah locus include an increased susceptibility to chemical carcinogenesis, mutagenicity in vitro, and drug toxicity--manifested as hepatic necrosis, aplastic anemia, or shortened survival time. Pregnant mice received a single injection of 3-methylcholanthrene or 7,12-dimethylbenz[a] anthracene between day 5 and day 13 of gestation, and the uterine contents were examined on day 18. Striking increases were observed in the incidence of MC-1 and DMBA-induced resorptions and congenital malformations in the aromatic hydrocarbon "responsive" C57BL/6N inbred strain, and of DMBA-induced resorptions in the "responsive" C3H/HeN and BALB/cAnN strains--when compared with the similarly treated genetically "nonresponsive" AKR/N strain. These data suggest but do not prove that an association exists between the Ah locus and developmental toxicity, i.e., teratogenesis. Although numerous teratogenic differences among inbred mouse strains have previously reported, this study is unique in that the genetic differences in teratogenicity observed were predicted in advance on the basis of known differences among these strains in polycyclic hydrocarbon metabolism regulated by the Ah locus.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2026

Integrated experimental and bioinformatics analysis reveals ECM-integrin and redox signaling associated with PMMA/NiO nanocomposites for craniofacial applications.

BACKGROUND: Poly(methyl methacrylate) (PMMA) is widely used in dental and craniofacial applications; however, its clinical performance is limited by poor surface wettability, moderate mechanical strength, and restricted biological activity. Integrating nanomaterial engineering with computational biology offers an opportunity to better understand biomaterial-cell interactions and support the rational design of functional biomaterials. METHODS: Nickel oxide (NiO) nanoparticles were synthesized via chemical precipitation and incorporated into PMMA to fabricate nanocomposites. Physicochemical characterization included contact angle measurements, Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and Vickers hardness testing. Biocompatibility was evaluated using zebrafish embryo developmental assays. To explore biological processes potentially associated with biomaterial-cell interactions, bioinformatics analyses including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and STRING protein-protein interaction (PPI) network analyses were performed. RESULTS: Incorporation of NiO nanoparticles improved the surface and mechanical properties of PMMA, reducing the contact angle from 105.35° to 90.46° and increasing Vickers hardness compared with unmodified PMMA. Structural and morphological analyses confirmed successful synthesis and homogeneous nanoparticle incorporation. Zebrafish embryo studies demonstrated minimal developmental toxicity, supporting the biocompatibility of the nanocomposite. Bioinformatics analyses identified significant enrichment of pathways related to extracellular matrix organization, cell adhesion, focal adhesion, PI3K-Akt signaling, and oxidative stress regulation. Protein-protein interaction analysis revealed highly interconnected networks associated with ECM-integrin signaling and redox homeostasis, highlighting biological processes potentially associated with biomaterial-cell communication. CONCLUSIONS: PMMA/NiO nanocomposites exhibited improved physicochemical performance and favorable biocompatibility characteristics. The integration of experimental characterization with bioinformatics and network-based analyses provides a systems-level perspective on biomaterial-associated cellular processes and identifies ECM-integrin signaling and oxidative stress-related pathways as candidate biological processes for future experimental validation. These findings support the continued development of PMMA/NiO nanocomposites for oral and craniofacial biomedical applications.

Nanocomposites↗
PubMed2026

Hydrogen-supported biodefluorination of unsaturated perfluorinated carboxylic acids.

PFMeUPA (i.e., (E)-perfluoro(4-methylpent-2-enoic acid) is a unsaturated perfluorohexanoic acid wtih emerging concern due to its potential to cause developmental toxicity. Here, we investigate the sustainable biological treatment of PFMeUPA under anoxic conditions by delineating batch degradation potential and continuous-flow reactor dynamics using hydrogen (H2) as the sole electron donor. In batch assays inoculated with anaerobic digestion sludge, an enriched hydrogenotrophic consortium achieved near-complete removal of 50 μM PFMeUPA over 90-days with a stoichiometric release of 125 μM fluoride (F-), representing a 26% defluorination extent that corresponds to the cleavage of two C-F bonds per molecule. The continuous-flow H₂-based membrane biofilm reactor (MBfR) harboring this enriched anaerobic biofilm was operated for 130 days, achieving 100% removal of 5 μM PFMeUPA and 20% of defluorination at a hydraulic retention time (HRT) = 6 h. Transformation product identification using high-resolution mass spectrometry suggests dominance of reductive defluorination and a shift toward hydrogenated byproducts at later stages. Metagenomic results indicate the enrichment of microbial taxa including Hydrogenophaga (hp_bin.22) and and Azonexus (hp_bin.19) genomes, which carry genes for hydrogen metabolism (hoxH) and fluoride efflux pumps (crcB). This work demonstrates the feasibility of hydrogen-supported biological treatment for unsaturated perfluorinated carboxylic acids from contaminated water. SYNOPSIS: We demonstrate reductive defluorination of branched PFAS by a H2-fed biofilm, with co-occurring hydrogenase and fluoride exporter genes in Hydrogenophaga and Azonexus as potential biodefluorination biomarkers.

Hydrogenotrophic biodefluorination↗
PubMed2026

Environmental benzene exposure induces a conserved neutrophil degranulation program across species.

Immune systems have evolved under constant pressure from pathogens and environmental challenges, leading to the emergence of conserved defense mechanisms across diverse organisms. Evidence indicates that environmental exposures perturb immune regulatory networks, particularly during development, when transcriptional programs governing hematopoiesis, immune cell differentiation, and inflammatory signaling are highly dynamic and sensitive to external stressors. Volatile organic compounds represent an important but incompletely understood source of immunological perturbation. Among these, benzene is a ubiquitous environmental contaminant associated with hematotoxicity and immune dysregulation; however, transcriptional responses to environmentally relevant low-level exposures during development remain poorly characterized. To determine whether benzene exposure engages conserved cross-species immune regulatory pathways, we performed a comparative transcriptomic analysis integrating developmental tissues from 3 vertebrate systems: human placenta, murine placenta, and zebrafish larvae. Bulk RNA sequencing datasets were analyzed to identify transcriptional responses associated with benzene exposure in experimental models (≤5 ppm) and with benzene adduct levels in maternal plasma for human samples. Because placental gene expression exhibits strong sexual dimorphism, murine datasets were stratified by fetal sex. Pathway- and network-level analyses were used to identify conserved biological responses. We observed a striking convergence on activation of innate immune pathways associated with neutrophil degranulation, IL-8 signaling, and Rho GTPase-mediated inflammatory responses. Further, network analyses identified CXCL8 and ERK1/2 as shared regulatory hubs linking transcriptional responses across datasets. Together, these findings uncover an evolutionarily conserved innate immune signature associated with benzene exposure during vertebrate development, suggesting that environmental chemical perturbations may disrupt fundamental immune regulatory programs across species.

Animals↗
PubMed2026

The maternal-to-zygotic transition is a critical window for PFOA-induced disruption of developmental programming.

Early embryogenesis is governed by precisely timed gene regulatory programs that coordinate cell fate specification, tissue patterning, and morphogenesis. The maternal-to-zygotic transition (MZT) represents a pivotal developmental milestone during which regulatory control shifts from maternally deposited transcripts to activation of the zygotic genome. Disruption of this transition has the potential to alter developmental trajectories with lasting consequences. Per- and polyfluoroalkyl substances (PFAS), environmentally persistent contaminants, have been linked to developmental abnormalities, yet their impact on core embryonic gene regulatory networks especially with exposure during MZT is not well understood. Using zebrafish (Danio rerio), a tractable vertebrate model and New Approach Methodology (NAM), we investigated how PFAS exposure during the MZT alters early developmental programming. Embryos were exposed starting at different times before and within the MZT time window and collected at 24 h post-fertilization (hpf) for transcriptomic analysis. Targeted qRT-PCR revealed dysregulation of genes controlling transcriptional activation, lineage specification, proliferation, and differentiation. Whole-transcriptome RNA sequencing (RNA-seq) further identified widespread perturbations in gene networks governing transcriptional regulation, cell signaling, and embryonic morphogenesis. Temporal analysis revealed that exposure beginning at 3.5 hpf, followed by 8 hpf, corresponding to early zygotic genome activation and near completion of zygotic activation, respectively, resulted in the greatest differential gene expression changes at 24 hpf. Consistent with these early gene regulatory perturbations, larvae exposed starting at 8 hpf also exhibited altered behavior at 5 days post-fertilization. Together, these findings demonstrate that PFAS exposure during MZT disrupts the establishment of embryonic gene regulatory networks, linking environmental toxicant exposure to altered developmental patterning and organismal outcomes. This work underscores the vulnerability of early developmental transitions to environmental perturbation and positions MZT as a critical window of susceptibility during development.

NAMs (new approach methodologies)↗
PubMed2025

Exposure to zinc oxide nanoparticles inhibits preimplantation embryonic development by disrupting zygotic genome activation.

The potential adverse effects of zinc oxide nanoparticles (ZnONPs) on human reproductive health may arise from their increasing industrial and commercial applications. However, their effects on preimplantation embryonic development and the related molecular mechanisms are still not well understood. Here, we demonstrate that ZnONPs exposure exhibit toxicity to a critical developmental period in mice. We observed that sustained exposure to ZnONPs in vitro resulted in embryonic development arrest at the 2-cell stage. To identify the susceptible stage, we controlled experiments to treat embryos with ZnONPs in the different processes of early embryonic development and determined that ZnONPs mainly to affect 2-cell stage embryos. According to the RNA-seq and EU (5-ethynyl uridine) analysis, the transcriptional activity of minor ZGA genes increased in the late 2-cell embryos following ZnONPs exposure. Subsequently, we employed multi-omics assays, including CUT&Tag and ATAC-seq. We found that ZnONPs exposure led to increased enrichment of H3K27ac (Histone H3 acetylated lysine 27) in late 2-cell embryos and enhanced chromatin accessibility, which led to abnormal upregulation of minor zygotic genome activation (ZGA) genes. In addition, the direct occupancy of ZnONPs at H3K27ac modification sites was verified through pulldown and immunoprecipitation. In conclusion, our findings demonstrate that ZnONPs exposure disrupting minor ZGA by interfering with H3K27ac erasure on the embryonic genome and ultimately impairing the developmental potential of embryos.

Animals↗
PubMed2026

Maternal transfer of nonylphenol drives oxidative, immune, and epigenetic dysregulation in zebrafish offspring.

Nonylphenol (NP), a widespread surfactant and endocrine-disrupting pollutant, poses significant ecological and public health risks globally; however, its transgenerational effects remain poorly understood. Using zebrafish (Danio rerio), we compared chronic maternal NP exposure (50 and 100 µg/L, 28 days) with acute embryonic exposure (0.22 µmol/L) during 0-3 days post-fertilization (dpf) to delineate mechanistic differences in toxicity. Maternal NP exposure produced severe developmental defects in offspring, including edema, axial curvature, impaired swim bladder inflation, reduced growth, cardiac dysfunction, and decreased viability. These phenotypes were accompanied by systemic molecular disruptions including oxidative stress, altered estrogen receptor (ER) expression, dysregulated mitogen-activated protein kinase (MAPK) signaling, and suppressed innate immune response characterized by attenuated neutrophil/macrophage density, reduced CD68 and complement protein C3 expression, diminished nitrite load, and downregulation of pro-inflammatory mediators at both transcript and protein levels. Maternal exposure further induced apoptosis and persistent epigenetic reprogramming (alterations in DNA methylation and histone-modifying enzymes), hallmarks of transgenerational toxicity. In contrast, direct embryonic NP exposure elicited morphological abnormalities without significant lethality, accompanied by induction of pro-inflammatory cytokines, nitric oxide (NO) synthesis, and MAPK activation, reflecting an augmented inflammatory response. These mechanistic contrasts reveal that maternal NP exposure is a potent driver of systemic, heritable molecular reprogramming, whereas embryonic exposure triggers acute inflammatory pathways. Together, our findings underscore the global relevance of NP as a transgenerational toxicant, advocating for its urgent inclusion in ecotoxicological risk assessments and regulatory frameworks.

Animals↗
PubMed1979

Toxicity of selenium to developing Xenopus laevis embryos.

Se in the form of sodium selenite is toxic to Xenopus laevis embryos and tadpoles continuously exposed to concentrations above 1 ppm. Concentrations of 2 ppm and above result in severe developmental abnormalities and increased mortality. Uptake and loss of radioactive Se from water are rapid, but depuration is not complete indicating that some Se can remain bound by the organism. The facts that Se is toxic at low levels to Xenopus embryos and tadpoles, can cause developmental abnormalities, and accumulates in tissues suggest that increased release of Se compounds into the environment poses a potential threat to aquatic organisms.

Abnormalities, Drug-Induced↗
PubMed1977

Variation in the direction of selection applied by pentenol to the alcohol dehydrogenase locus in Drosophila melanogaster.

This paper describes selective effects of pentenol-impregnated media on six genotypes at the alcohol dehydrogenase (Adh) locus in D. melanogaster. In the laboratory population studied, developmental times of pre-adults homozygous for an alcohol dehydrogenase "null" allele increased with increasing pentenol concentrations. The developmental times of the other five genotypes, which produced active alcohol dehydrogenases, increased slightly at pentenol concentrations up to 0-0033%, but above this concentration they decreased markedly. In fact on 0-067% pentenol, the highest concentration tested, developmental times of these five genotypes were between 9 and 24 h less than their developmental times on media lacking pentenol. The magnitude of the reduction in developmental time differed significantly between genotypes and was positively correlated with alcohol dehydrogenase activity. Pentenol had toxic effects on adults and significant differences were found between survival percentages of adults of different genotypes on pentenol-impregnated media. These survival percentages were negatively correlated with alcohol dehydrogenase activities. Therefore selective differences between genotypes in adult survival were negatively correlated with those in developmental times. The variations in the direction of selection are discussed in terms of their possible biochemical basis and their effects on the maintenance of Adh polymorphisms.

Alcohol Oxidoreductases↗