Transgenerational nanoplastic toxicity could be detected in Caenorhabditis elegans after exposure at the parental generation (P0-G); however, the underlying mechanisms remain largely unclear. We aimed to examine the role of germline nuclear hormone receptors (NHRs) in controlling the transgenerational toxicity of polystyrene nanoparticles (PS-NPs) based on gene expression screening and functional analysis. Among germline NHR genes, daf-12, nhr-14, and nhr-47 expressions were increased and nhr-12 expression was decreased by PS-NPs (1 and 10 μg/L). Transgenerational alterations in expressions of these four NHR genes were also induced by PS-NPs (1 and 10 μg/L). RNAi of daf-12, nhr-14, and nhr-47 caused resistance, whereas RNAi of nhr-12 conferred susceptibility to transgenerational PS-NP toxicity. After PS-NP exposure, expressions of ins-3, daf-28, and ins-39 encoding insulin ligands, efn-3 encoding Ephrin ligand, and lin-44 encoding Wnt ligand, as well as expressions of their receptor genes (daf-2, vab-1, and/or mig-1), were dysregulated by the RNAi of daf-12, nhr-14, nhr-47, and nhr-12. Therefore, alteration in certain germline NHRs could mediate the induction of transgenerational nanoplastic toxicity by affecting secreted ligands and their receptors in the offspring of exposed organisms.

Neonicotinoid pesticides (NNs) transfer rapidly from mother to offspring, which exhibit neurobehavioral effects. However, no studies have investigated NNs\' transgenerational effects. We exposed F0 generation mice (mothers) to a no-observed-adverse-effect level (NOAEL) of clothianidin (CLO) during gestation and lactation, and examined the adult neurobehavioral effects of three generations of offspring (F1, F2, F3). F1 had lower birth weight, decreased locomotor activity, and increased anxiety-like behavior. In F2, body weight was affected, and there was a decreasing trend in locomotor activity and an increasing trend in anxiety-like behavior. In F3, locomotor activity tended to increase. Thus, even when only the mothers were exposed, the effects of CLOs were still observed in F1, F2, and F3 but the effects became smaller.

Recently, the transgenerational toxicity of nanoplastics has received increasing attention. Caenorhabditis elegans is a useful model to assess the transgenerational toxicity of different pollutants. In nematodes, the possibility of early-life exposure to sulfonate-modified polystyrene nanoparticle (PS-S NP) causing transgenerational toxicity and its underlying mechanisms were investigated. After exposure at the L1-larval stage, transgenerational inhibition in both locomotion behavior (body bend and head thrash) and reproductive capacity (number of offspring and fertilized egg number in uterus) was induced by 1-100 μg/L PS-S NP. Meanwhile, after exposure to 1-100 μg/L PS-S NP, the expression of germline lag-2 encoding Notch ligand was increased not only at the parental generation (P0-G) but also in the offspring, and the transgenerational toxicity was inhibited by the germline RNA interference (RNAi) of lag-2. During the transgenerational toxicity formation, the parental LAG-2 activated the corresponding Notch receptor GLP-1 in the offspring, and transgenerational toxicity was also suppressed by glp-1 RNAi. GLP-1 functioned in the germline and the neurons to mediate the PS-S NP toxicity. In PS-S NP-exposed nematodes, germline GLP-1 activated the insulin peptides of INS-39, INS-3, and DAF-28, and neuronal GLP-1 inhibited the DAF-7, DBL-1, and GLB-10. Therefore, the exposure risk in inducing transgenerational toxicity through PS-S NP was suggested, and this transgenerational toxicity was mediated by the activation of germline Notch signal in organisms.

Nanoplastic exposure can potentially cause the severe transgenerational toxicity in organisms. However, the transgenerational nanoplastic toxicity and the underlying mechanisms are still largely unclear. Using Caenorhabditis elegans as an animal model, we here compared the transgenerational toxicity of two sizes of polystyrene nanoparticles (PS-NPs, 20 and 100 nm). The nematodes were exposed to PS-NPs at the P0 generation, and from the F1 generation the nematodes were grown under the normal condition. Exposure to 20 nm PS-NPs resulted in more severe transgenerational toxicity than exposure to 100 nm PS-NPs. At the concentration of 100 μg/L, the toxicity of 20 nm PS-NPs on locomotion and reproduction was detected at the F1-F6 generations, whereas the toxicity of 100 nm PS-NPs could only be observed at the F1-F3 generations. The difference in transgeneration toxicity between PS-NPs (20 nm) and PS-NPs (100 nm) was associated with the difference in transgenerational activation of oxidative stress. Based on observations on SOD-3::GFP, HSP-6::GFP, and HSP-4::GFP expressions, PS-NPs (20 nm) and PS-NPs (100 nm) further induced different transgenerational responses of anti-oxidation, mt UPR, and ER UPR. Our data suggested that the induction of transgenerational toxicity of PS-NPs was size dependent in nematodes. The results are helpful for our understanding the cellular mechanisms for the induction of transgenerational nanoplastic toxicity in organisms.

Certain modifications can aggravate the toxicity of nanoplastics. However, the influence of surface amino modification on transgenerational impairment induced by nanoplastics remains largely unclear. Pristine nanopolystyrene (NPS) and amino modified NPS (NPS-NH2) were used to determine their transgenerational toxicity in Caenorhabditis elegans. Exposure to 100 μg/L pristine NPS in parents (P0) cause a decrease in reproductive capacity in the F1-F3 generations and the damage on gonad development in the F1-F2 generations. In contrast, exposure to 10 μg/L NPS-NH2 caused toxicity on reproductive capacity and gonad development in the F1 generation. The toxic effects of NPS-NH2 on reproductive capacity and gonad development in the F1-F3 generations were more severe than those of pristine NPS. Moreover, amino modification could increase transgenerational toxicity of NPS in inducing apoptosis of germline and in affecting expressions of ced-1, ced-4, and ced-9. Our data demonstrate that surface modification of NPS with amino groups enhances transgenerational reproductive toxicity of NPS in C. elegans.

Methamphetamine (METH) has been recognized as an emerging organic contaminant as it was widely detected in the aquatic environment via wastewater effluent discharge. However, the ecological hazard posed by METH at environmentally relevant concentrations was remained unclear. In this study, adult medaka fish were exposed to METH at environmental levels (0.05, 0.2, 0.5, 5 μg L-1) and high level (25 and 100 μg L-1) for 90 days to investigate its effect on ecologically behavioral functions, histopathology, bioconcentration, and transgenerational toxicity. The significant increase of locomotion activity, total distance, and max velocity of adult medaka were observed at low METH levels (0.2-0.5 μg L-1), while it markedly decreased at high levels (25-100 μg L-1). This effect may increase the predation risk of the fish. The significant alteration on the relative expressions of the genes (cacna1c, oxtr, erk1, and c-fos), as well as the contents of the proteins (oxytocin (OXT) and protein kinase A (PKA)) involved in Voltage Dependent Calcium Channel (VDCC) and Mitogen-Activated Protein Kinase (MAPK) signaling channel induced by METH could partly elucidate the underlying mechanisms of the changes of the behavioral traits. METH could induce obvious minimal gliosis, neuronal loss, and necrotic in brain tissues. Additionally, the significant increase of hepatic-somatic index (HSI) of male medaka at 0.2-5 μg L-1 groups, and the decrease of female medaka at 100 μg L-1 group indicated male fish was more susceptible to METH. Nephric-somatic index (NSI) of medaka markedly declined induced by METH at 0.05-100 μg L-1. The bioconcentration factor (BCF) (0.4-5.8) in medaka fish revealed the bioconcentration potential of METH in fish. This study for the first time demonstrated METH could induced the development defects of larvae in F1 generation at environmentally relevant concentrations, thereby resulting in a significant decrease in the capacity of fish to produce offspring. Meanwhile, the RQ values (>1) of METH in river in China, USA, and Australia showed a high teratogenic risk level, suggesting the ecosystem-levels consequence posed by METH should be concerned.

Cadmium (Cd) is a heavy metal of concern in contaminated sites because of its high toxicity to soil biota and humans. Typically, Cd exposure is thought to be dominated by dissolved Cd in soil pore water and, thus, dermal uptake. In this study, we investigated the uptake, toxicity, and maternal transfer of Cd in a standard soil invertebrate, the oribatid mite (Oppia nitens), which is common to boreal and temperate ecozones. We found total soil Cd predicted Cd uptake in adult and juvenile O. nitens with no significant uptake from pore water by juvenile mites. Cadmium significantly inhibited juvenile production and recruitment as well as reduced adult fecundity. Adult O. nitens maternally transferred 39-52% of their Cd body burden to juveniles (tritonymphs) while the maternally-acquired Cd accounted for 41% of the juvenile internal Cd load. Our results suggest that dermal adsorption of metal ions is not important for O. nitens and that maternal transfer of Cd in soil invertebrates has ecological and toxicological implications for populations of soil invertebrates. Maternal transfer should be incorporated as a criterion in setting environmental soil quality guidelines (SQGE) for cadmium and other non-essential heavy metals.

As a Chinese-specific alternative to perfluorooctane sulfonate (PFOS), 6:2 chlorinated polyfluorinated ether sulfonate (commercial name: F-53B) has been used in the metal plating industry for over 40 years. This prevalence of use has resulted in its subsequent detection within the environment, wildlife, and humans. Despite this, however, its hepatotoxic effects on aquatic organisms remain unclear. Here, we characterized the impacts of long-term F-53B exposure on adult zebrafish liver and their offspring. Results showed that the concentration of F-53B was greater in the F0 liver than that in the gonads and blood. Furthermore, males had significantly higher liver F-53B levels than females. Hepatomegaly and obvious cytoplasmic vacuolation indicated that F-53B exposure induced liver injury. Compared to control, liver triglyceride levels decreased by 30% and 33.5% in the 5 and 50 μg/L-exposed males and 22% in 50 μg/L-exposed females. Liver transcriptome analysis of F0 adult fish found 2175 and 1267 differentially expressed genes (DEGs) in the 5 μg/L-exposed males and females, respectively. Enrichment analyses further demonstrated that the effects of F-53B on hepatic transcripts were sex-dependent. Gene Ontology showed that most DEGs were involved in multicellular organism development in male fish, whereas in female fish, most DEGs were related to metabolic processes and gene expression. qRT-PCR analysis indicated that the PPAR signaling pathway likely contributed to F-53B-induced disruption of lipid metabolism in F0 adult fish. In F1 larvae (5 days post fertilization), the transcription of pparα increased, like that in F0 adult fish, but most target genes showed the opposite expression trends as their parents. Taken together, our research demonstrated chronic F-53B exposure adversely impacts zebrafish liver, with disruption of PPAR signaling pathway dependent on sex and developmental stage.

Although 6:2 chlorinated polyfluorinated ether sulfonate (F-53B), an alternative to perfluorooctanesulfonate (PFOS), has been regularly detected in different environmental matrices, information regarding its toxicity remains limited. To explore the transgenerational thyroid-disrupting capacity of F-53B, adult zebrafish (F0) were exposed to different concentrations of F-53B (0, 5, 50, or 500μg/L) for 180d, with their offspring (F1 and F2) subsequently reared in uncontaminated water. Thyroid disturbances were then examined in the three (F0, F1, and F2) generations. For F0 adult fish, thyroxine (T4) increased in both sexes after exposure to 50μg/LF-53B, whereas 3,5,3\'-triiodothyronine (T3) decreased in all groups, except for 50μg/LF-53B-treated males. For F1 embryos, parental exposure resulted in F-53B transfer as well as an increase in T4 content. At 5days post-fertilization, the significant increase in T4 and decrease in T3 were accompanied by a decrease in body length, increase in mortality, and increase in uninflated posterior swim bladder occurrence in F1 larvae. Although thyroid hormone levels were not changed significantly in F1 adult fish or F2 offspring compared with the control, the transcription levels of several genes along the hypothalamus-pituitary-thyroid axis were significantly modified. Our study demonstrated that F-53B possesses transgenerational thyroid-disrupting capability in zebrafish, indicating it might not be a safer alternative to PFOS.

In this study, the effects of both continuous and alternate exposure to 2 mg L-1 of flumequine (FLU) on survival, growth and reproduction of Daphnia magna were evaluated over four generations. Mortality was the most evident effect, with an average mortality rate of 23 ± 14% across generations. Individuals destined to succumb were identifiable well in advance through their discolouration and lack of development, and limited or zero reproductive capacity. Inhibition of reproduction in surviving mothers varied across the four generations (14.3 ± 17%) without an apparent correlation with the duration of exposure over generations. Significant reproductive inhibition was observed in the generation that followed three non-exposed generations (the fourth generation), pointing to a transgenerational toxicity of FLU. In another experiment, in vitro exposure of 72 D. magna embryos to 2 mg L-1 FLU caused 14% mortality (versus 7% in the control). Among the 62 individuals that hatched alive, six showed birth defects and only one was able to survive the next few days. The other, apparently healthy newborns were randomly assigned to two groups and submitted to a reproduction test, either in the absence or in the presence of 2 mg L-1 FLU. A high mortality rate and/or strongly significantly inhibited reproduction were detected in both groups. As with previously run analogous tests with enrofloxacin, the multigenerational and embryonic tests showed a clear disruption to this crustacean population which would not be evidenced by the standard official acute and chronic tests. This indicates the necessity of taking a different and more comprehensive approach to the evaluation of substances having an inherent ability to interact with genetic material.