Intergenerational toxicity of 17α-ethinylestradiol (EE2): Effects of parental exposure on early larval development and transcriptomic profiles in the Sydney rock oyster, Saccostrea glomerata.

This study exposed adult Sydney rock oysters, of either sex or both, to the synthetic estrogen 17α-ethinylestradiol (EE2) at 50 ng/L for 21 days, followed by an examination of developmental endpoints and transcriptomic responses in unexposed larvae. Reduced survival was observed at 1 day post-fertilisation (dpf) in larvae from bi-parental exposure (FTMT). Motile larvae at 2 dpf were fewer from maternal (FTMC), paternal (FCMT), and FTMT exposures. Additionally, shell length at 7 dpf decreased in larvae from FTMC and FTMT parents. RNA sequencing (RNA-seq) revealed 1064 differentially expressed genes (DEGs) in 1-dpf larvae from FTMT parents, while fewer DEGs were detected in larvae from FTMC and FCMT parents, with 258 and 7, respectively. GO and KEGG analyses showed significant enrichment of DEGs in diverse terms and pathways, with limited overlap among treatment groups. IPA results indicated potential inhibition of pathways regulating energy production, larval development, transcription, and detoxification of reactive oxygen species in FTMT larvae. qRT-PCR validation confirmed significant downregulation of selected DEGs involved in these pathways and relevant biological processes, as identified in the RNA-seq dataset. Overall, our results suggest that the intergenerational toxicity of EE2 is primarily maternally transmitted, with bi-parental exposure amplifying these effects.

Intergenerational toxic effects of 1-methyl-3-octylimidazolium chloride and 1-dodecylpyridinium chloride on the water flea, Moina macrocopa.

Ionic liquids (ILs) are generally considered eco-friendly alternatives to conventional industrial solvents, but they are hard to degrade and easily accumulate in the environment. Therefore, their long-term toxicities are especially vital to estimate their potential risk. However, the chronic toxicities of ILs over generations lacked intensive investigation. In the present work, acute toxicity and chronic toxicity of 1-methyl-3-octylimidazolium chloride ([Omim]Cl) and 1-dodecylpyridinium chloride ([DPy]Cl) were studied on Moina macrocopa with the first exposed generation (F0) and two successive recovery generation (F1 to F2). The acute results showed that both [Omim]Cl and [DPy]Cl exhibited high toxicity to M. macrocopa. The chronic results indicated that the exposure of [Omim]Cl and [DPy]Cl could inhibit the survivorship, body length, and reproduction of M. macrocopa and exhibited a significant dose-related decrease. Furthermore, these two types of ILs presented intergenerational toxicity in the water flea. And the toxic effects of [Omim]Cl disappeared in the recovery tests of F2 generation, while the [DPy]Cl toxic effects continued. Our research suggested a potential risk for the aquatic ecosystem induced by ILs. And the damage done by these chemicals to the aquatic environment is worthy of attention.

Chronic Paternal/Maternal Exposure to Environmental Concentrations of Imidacloprid and Thiamethoxam Causes Intergenerational Toxicity in Zebrafish Offspring.

Imidacloprid (IMI) and thiamethoxam (THM) are ubiquitous in aquatic ecosystems. Their negative effects on parental fish are investigated while intergenerational effects at environmentally relevant concentrations remain unclear. In this study, F0 zebrafish exposed to IMI and THM (0, 50, and 500 ng L-1) for 144 days post-fertilization (dpf) was allowed to spawn with two modes (internal mating and cross-mating), resulting in four types of F1 generations to investigate the intergenerational effects. IMI and THM affected F0 zebrafish fecundity, gonadal development, sex hormone and VTG levels, with accumulations found in F0 muscles and ovaries. In F1 generation, paternal or maternal exposure to IMI and THM also influenced sex hormones levels and elevated the heart rate and spontaneous movement rate. LncRNA-mRNA network analysis revealed that cell cycle and oocyte meiosis-related pathways in IMI groups and steroid biosynthesis related pathways in THM groups were significantly enriched in F1 offspring. Similar transcriptional alterations of dmrt1, insl3, cdc20, ccnb1, dnd1, ddx4, cox4i1l, and cox5b2 were observed in gonads of F0 and F1 generations. The findings indicated that prolonged paternal or maternal exposure to IMI and THM could severely cause intergenerational toxicity, resulting in developmental toxicity and endocrine-disrupting effects in zebrafish offspring.

Chronic and intergenerational toxic effects of 1-decyl-3-methylimidazolium hexafluorophosphate on the water flea, Moina macrocopa.

With the increasing use and production of "green solvents" ionic liquids (ILs) and their known stability in the environment, the potential adverse effects of ILs have become a focus of research. In the present study, acute, chronic, and intergenerational toxic effects of an imidazolium-based ionic liquid, 1-decyl-3-methylimidazolium hexafluorophosphate ([Demim]PF6), on Moina macrocopa were investigated following the parental exposure. The results showed that [Demim]PF6 exhibited high toxicity to M. macrocopa, and the long-term exposure significantly inhibited the survivorship, development, and reproduction of the water flea. Furthermore, it is also observed that [Demim]PF6 induced toxic effects in the following generation of M. macrocopa, resulting in the complete cessation of reproduction in the first offspring generation, and the growth of the organisms was also significantly affected. These findings provided a novel insight into the intergenerational toxicity induced by ILs to crustaceans and suggested that these compounds pose potential risks to the aquatic ecosystem.

Intergenerational toxic effects of parental exposure to [Cn mim]NO3 (n = 2,4,6) on nervous and skeletal development in zebrafish offspring.

Ionic liquids (ILs) are thought to have negative effects on human health. Researchers have explored the effects of ILs on zebrafish development during the early stages, but the intergenerational toxicity of ILs on zebrafish development has rarely been reported. Herein, parental zebrafish were exposed to different concentrations (0, 12.5, 25, and 50 mg/L) of [Cn mim]NO3 (n = 2, 4, 6) for 1 week. Subsequently, the F1 offspring were cultured in clean water for 96 h. [Cn mim]NO3 (n = 2, 4, 6) exposure inhibited spermatogenesis and oogenesis in F0 adults, even causing obvious lacunae in the testis and atretic follicle oocytes in ovary. After parental exposure to [Cn mim]NO3 (n = 2, 4, 6), the body length and locomotor behavior were measured in F1 larvae at 96 hours post-fertilization (hpf). The results showed that the higher the concentration of [Cn mim]NO3 (n = 2, 4, 6), the shorter the body length and swimming distance, and the longer the immobility time. Besides, a longer alkyl chain length of [Cn mim]NO3 had a more negative effect on body length and locomotor behavior. RNA-seq analysis revealed several downregulated differentially expressed genes (DEGs)-grin1b, prss1, gria3a, and gria4a-enriched in neurodevelopment-related pathways, particularly the pathway for neuroactive ligand-receptor interaction. Moreover, several upregulated DEGs, namely col1a1a, col1a1b, and acta2, were mainly associated with skeletal development. Expression of DEGs was tested by RT-qPCR, and the outcomes were consistent with those obtained from RNA-Seq. We provide evidence showing the effects of parental exposure to ILs on the regulation of nervous and skeletal development in F1 offspring, demonstrating intergenerational effects.

Intergenerational effects of parental [Cnmim]BF4 (n = 4, 6, 8) ionic liquids exposure on zebrafish development based on transcriptomic analysis.

Ionic liquids (ILs) have been developed as alternatives to traditional solvents, and their toxicity may be affected by alkyl chain length. Currently, there is limited evidence for whether parental exposure to different alkyl chain length ILs will induce intergenerational toxicity in zebrafish offspring. To address this knowledge gap, the parental zebrafish (F0) were exposed to 25 mg/L [Cnmim]BF4 (n = 4, 6, 8) for 7 days. Following this, fertilized F1 embryos from the exposed parents were reared in clean water for 120 h. Increased mortality, higher deformity rate, increased pericardial edema rate, and a shorter swimming distance and average speed were detected in the unexposed F1 embryonic larvae from the exposed F0 compared to the F1 generation from the unexposed F0. Parental exposure to [Cnmim]BF4 (n = 4, 6, 8) resulted in cardiac malformations and dysfunction in F1 larvae, including increased pericardial areas, increased yolk sac areas and decreased heart rate. Moreover, the intergenerational toxicity of [Cnmim]BF4 (n = 4, 6, 8) in F1 offspring appeared to be alkyl chain length-dependent. Parental [Cnmim]BF4 (n = 4, 6, 8) exposure led to global transcriptomic changes involved in developmental processes, nervous system process, cardiomyopathy, cardiac muscle contraction, and metabolic signalling pathways such as PI3K-Akt, PPAR and cAMP pathways in unexposed F1 offspring. Overall, the present study provides evidence that the neurotoxicity and cardiotoxicity of ILs in zebrafish can be markedly transmitted to offspring, and the intergenerational developmental toxicity is probably linked to transcriptomic alterations, highlighting the necessity of assessing ILs' environmental safety and human health risks.

Transcriptomic analysis of lipid metabolism in zebrafish offspring of parental long-term exposure to bisphenol A.

Bisphenol A (BPA) is one of the most common environmental endocrine disruptor chemicals (EDCs) and exhibits reproductive, cardiovascular, immune, and neurodevelopmental toxic effects. The development of the offspring was examined in the present investigation to determine the cross-generational effects of long-term exposure of parental zebrafish to environmental concentrations of BPA (15 and 225 µg/L). Parents were exposed to BPA for 120 days, and their offspring were evaluated at 7 days after fertilization in BPA-free water. The offspring exhibited higher mortality, deformity, and heart rates, and showed significant fat accumulation in abdominal region. RNA-Seq data showed that more lipid metabolism-related KEGG pathways, such as the PPAR signaling pathway, adipocytokine signaling pathway, and ether lipid metabolism pathway were enriched in the 225 µg/L BPA-treated offspring compared to 15 µg/L BPA-treated offspring, indicating greater effects of high dose BPA on offspring lipid metabolism. Lipid metabolism-related genes implied that BPA is responsible for disrupting lipid metabolic processes in the offspring through increased lipid production, abnormal transport, and disruption of lipid catabolism. The present study will be helpful for further evaluation of the reproductive toxicity of environmental BPA to organisms and the subsequent parent-mediated intergenerational toxicity.

Intergenerational and biological effects of roxithromycin and polystyrene microplastics to Daphnia magna.

The influence of microplastics (MPs) on transgenerational effects of pharmaceuticals are drawing growing attention, however, whether aged process will alter the carrier effects of MPs were unknown. In this study, the intergenerational toxicity of single and combined exposure of polystyrene microplastics (PS-MPs) and roxithromycin (ROX) were investigated at the environmentally related concentrations, using Daphina magna as test organism. In the presence of UV-aged PS-MPs, the survival of D. magna for maternal generation (F0) at ROX concentration of 0.1 and 10 µg/L were increased by 20% and 40%, respectively. Meanwhile, the inhibition effects of ROX on the number of offspring and intrinsic rate of natural increase were obviously moderated. All these reproductive toxicity of ROX and PS-MPs in the first offspring (F1) were further aggravated both for the single and combined exposure. And the adverse effects disappeared much easier for the single exposure compared to the co-exposure through subsequent recovery. The combined exposure resulted in the change of inhibition of ROX on the swimming velocity and acceleration of D. magna into induction, while the feeding behavior kept inhibited. The AChE activity was distinctly increased by 1.61-3.25 times for the single and combined treatments, and the induction level of UV-aged MPs was higher than that of original MPs. Oxidative stress of the single exposure of ROX and original PS-MPs was observed with obvious induction of T-AOC and SOD activity, while the significant increase of MDA content was observed for the co-exposure. Among all indicators, the biochemical biomarkers and time of first brood were attributed to a class among all indicators, indicating that the time of first brood might be the most sensitive reproductive toxicity index. These results illustrated that both maternal impacts and offspring quality need to be considered for assessment of interaction of emerging contaminants.

Changes in defense capacity to infectious hematopoietic necrosis virus (IHNv) in rainbow trout intergenerationally exposed to glyphosate.

Glyphosate, the most widely used herbicide active substance worldwide, has raised many scientific, political and public debates in the context of its recent re-registration in the European Union, highlighting in particular a lack of data concerning its potential generational effects. In this study, we investigated the intergenerational toxicity of this active substance used alone or coformulated in glyphosate-based herbicides (GBHs) on the ability of rainbow trout (Oncorhynchus mykiss) to face a viral challenge. Juvenile trout from parents exposed for eight months to four different chemical exposure conditions (non-exposed control, pure glyphosate, Roundup Innovert®, and Viaglif Jardin® were experimentally infected with the infectious hematopoietic necrosis virus (IHNv). Various enzymatic and hemato-immunological markers were assessed before and after the viral challenge. Chemical contamination with GBHs strongly modulated viral trout susceptibility. Pure glyphosate induced a cumulative mortality of 35.8%, comparable to the control (37.0%), which was significantly reduced with Roundup Innovert® (-9.9%) and increased (+14.8%) with Viaglif Jardin®. No modification was observed for the biomarkers analysed for any conditions. These results demonstrate that the nature of the co-formulants associated to glyphosate in GHBs can modulate the susceptibility of fish to pathogens.

The mechanisms in the altered ontogenetic development and lung-related pathology in microcystin-leucine arginine (MC-LR)-paternal-exposed offspring mice.

A father's lifetime experience is a major risk factor for a range of diseases in an individual, and the consequences of the exposure can also be transmitted to his offspring. Our previous work has demonstrated that damage to testicular structures and decline in sperm quality in male mice can be caused by microcystin-leucine arginine (MC-LR), but the overall effects of the scope and extent of paternal exposure on health and disease in the offspring remain underexplored. Here, we report that MC-LR-paternal-exposed offspring mice showed reduced litter size and body weight accompanied by increased abnormalities in the lung. Analyses of the small noncoding RNAs (sncRNAs) in the sperm from MC-LR-exposed males demonstrated the downregulation of a wide range of piRNAs enriched for those target genes involved in the regulation of the embryo implantation pathways. Gene and protein expression analyses, as well as biochemical and functional studies, revealed suppressed expression of Hsp90α in testicular tissues from MC-LR-exposed males. Decreased Hsp90α in testicular tissues impaired the development of the offspring. In this study, we revealed that MC-LR alters the expression of Hsp90α in testicular tissues to cause changes in the expression profiles of sperm piRNAs produced by paternal mice. These changes lead to aberrant activation of the Wnt/ß-catenin signaling pathway in pulmonary tissues of offspring mice, causing lung tissue damage and abnormal development. We hereby confirmed that MC-LR-induced alterations in epigenetic inheritance are capable of contributing to intergenerational developmental defects in paternal-exposed offspring mice.