bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2022.06.14.496026

Life cycle exposure to cyhalofop-butyl induced reproductive toxicity toward zebrafish

Zhu, T.·Wang, S.·Li, D.
View original source ↗Export metadata ↓

Abstract

Cyhalofop-butyl (CyB) is an herbicide widely used in paddy fields, which may transfer to aquatic ecosystems and cause harm to aquatic organisms. In this study, zebrafish (Danio rerio) were exposed to CyB (0.1, 1 and 10 ug/L) related to the environment throughout its adult life cycle from embryo to sexual maturity. The effects of CyB on zebrafish growth, reproduction and offspring development were studied. It was found that female spawning was inhibited and adult male fertility decreased. In addition, we detected the expression of sex steroid hormones and genes related to hypothalamus-pituitary-gonad-liver (HPGL) axis. After 150days of exposure, the hormone balance of parent zebrafish (F0) was disturbed and the concentrations of 17{beta}-estradiol (E2) and vitellogenin (VTG) in zebrafish were decreased. F1 embryos showed abnormal developmental results, including decreased heart rate, decreased body length, spontaneous motor inhibition, while the developmental abnormalities of F1 embryos were relieved when exposed to CyB-free clear water. The change of sex hormone is regulated by gene expression related to HPGL axis. These results confirmed that long-term exposure to CyB in the environmental concentrations can damage the reproductive capacity of F0 generation zebrafish by disrupting the transcription of genes related to HPGL axis, which may lead to abnormal development of F1. Overall, these data may provide a new understanding of the reproductive toxicity of zebrafish parents and offspring after long-term exposure to CyB. HighlightsO_LIEnvironmental level of CyB exposure caused gonadal impairment. C_LIO_LICyB exposure suppressed spawning ability of zebrafish. C_LIO_LICyB exposure changed the plasma hormone level of zebrafish and altered HPGL axis in both genders. C_LIO_LIParental CyB exposure led to abnormal development of F1. C_LI

Explore related subjects

pharmacology and toxicologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Zhu, T., Wang, S., Li, D.. 2022-06-17. Life cycle exposure to cyhalofop-butyl induced reproductive toxicity toward zebrafish. https://doi.org/10.1101/2022.06.14.496026

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Lipid-ASO therapeutics exhibit differential tissue targeted delivery upon systemic or local CNS administration

Antisense oligonucleotides (ASOs) are a powerful therapeutic modality, but their full potential is hindered by pharmacokinetic properties that affect tissue and cellular delivery. Lipid conjugation is increasingly used to modulate ASO's biodistribution and promote extrahepatic activity, yet lipid dependent effects on in vivo functional delivery, particularly in the central nervous system (CNS), remain less explored. Here, we performed a side by side in vivo comparison of cholesterol, palmitic acid (C16:0), docosanoic acid (C22:0), and eicosapentaenoic acid (C20:5) conjugated to a fully phosphorothioated 3 10 3 LNA gapmer ASO targeting the Malat1 long non coding RNA. Lipid-ASO conjugates were administered systemically or locally in the brain of mice and evaluated for tissue level and cellular level distribution by imaging, qPCR and single-cell RNA sequencing, simultaneously annotating cell origin and global transcriptional changes within the cell. Following systemic administration in mice, lipid conjugation improved overall multi organ efficacy compared to unconjugated ASO, but with pronounced tissue specific differences. Single cell sequencing of liver and heart transcriptomes revealed lipid dependent cellular uptake patterns and transcriptional responses distinct from administration of unconjugated ASO. After intracerebroventricular administration, selected fatty acid conjugates enhanced silencing in deep brain regions such as the striatum, whereas cholesterol conjugation impaired functional delivery despite increased CNS retention. Light-sheet microscopy showed restricted parenchymal penetration of cholesterol ASOs compared with broader but heterogeneous distribution of palmitic acid conjugate. Together, these findings demonstrate that lipid identity critically determines ASO efficacy, productive cellular uptake, and regional CNS engagement, emphasizing the need for context specific lipid design in ASO therapeutic development.

pharmacology and toxicology↗
bioRxiv2026

Novel Dissymmetric Ionizable Lipid-Assembled Lipid Nanoparticles for Delivery of Ferroptosis-Related siRNA in Diabetic Treatment

Small interfering RNA (siRNA) enables precise post-transcriptional gene silencing for refractory diseases, yet its clinical translation remains limited by the lack of safe and efficient delivery vectors. Inspired by the dissymmetric alkyl chain architecture of natural membrane phospholipids, we designed and synthesized 34 novel ionizable lipids with dissymmetric hydrophobic tails and formulated them into lipid nanoparticles (LNPs). Through systematic physicochemical and biological assessments, we established clear structure-activity relationships and identified two lead LNPs (O14-LNP, H18a-LNP) with superior endosomal escape capacity, enhanced in vivo gene silencing potency, and favorable biosafety relative to the clinical benchmark MC3-LNP. In both streptozotocin-induced and spontaneous db/db type 2 diabetes (T2D) mouse models, lead LNPs delivering ferroptosis-related siRNAs effectively ameliorated glucose and lipid metabolic disorders, restored islet function, and alleviated hepatic steatosis. This study not only lays a theoretical foundation for the rational design of novel ionizable lipids, but also validates the therapeutic potential of siRNA therapy targeting ferroptosis, providing a versatile delivery platform and targeted therapeutic strategy for the treatment of T2D.

pharmacology and toxicology↗
bioRxiv2022

Composition efficacy of Unsaturated Arachidonic acid, Diterpenoids, Malvin (C29H35ClO17), and Bergenin to neutralise venom from different venomous snake species.

Snakebite envenomation is a serious problem in tropical and subtropical countries. Antivenom is the only treatment used to treat snake envenomation, however it is unable to neutralise local haemorrhage. Therefore, this studys aim is to evaluate the efficacy of P. dulce leaf extract to neutralise local haemorrhage induced by three clinically important snake species, B. jararaca, C. atrox and E. carinatus. Moreover, to determine the active components which are responsible for this activity. The plant leaves were extracted using different solvents, however, only E/e extract showed the best neutralizing capacity. The increasing doses, DF-1:2; 1:4, of E/e extract allowed better neutralizing ability s.c. In contrast, the oral/ i.p. acute toxicity test revealed that the optimal doses for the administration of E/e were 1 and 8 mg/kg. In addition to that, E/e was tested for its anti-lathality of LD50 using B. jararaca venom (1.1mg/kg) i.p., where the higher doses of 16 and 24 mg/kg killed 75% of BALB/C mice. Consequently, the different components of E/e extract were isolated with HPLC. The different components were grouped and tested to uncover the active ones. The results revealed that only three fractions were active, Frc11, Frc13, and Frc14. The active fractions showed a disparity in neutralizing the individual venoms, however, the best neutralising capacity was scored for Frc11. When the same fractions were pooled together, they showed a complete neutralizing ability against individual venoms as well as the pooled venoms. That was confirmed with the anti-gelatinase activity test, where pooled fraction inhibited the SVMP enzyme which is responsible for gelatinase activity. The phytochemical characterisation showed that the active fractions consist mainly of secondary metabolites such as tannins and polyphenols. MALDI-TOF MS confirmed the presence of secondary metabolites in the active fractions. The same fractions were tested for their anti-lethal activity using the pooled venoms (LD100), the results were statistically not significant, as all mice died including the positive controls. Nevertheless, the active fractions showed a noticeable increasing in survival time period especially Frc13 with an average survival time of 37 minutes. The positive control, IAV, scored the longest survival period with a gap of 11 minutes from Frc13.

pharmacology and toxicology↗