{"id":184,"title":"Paternal Preconception Calcitriol Intervention Rescued DBDPE-Induced Transgenerational Developmental and Visual Toxicity in Zebrafish","title_zh":"父源性孕前补充骨化三醇可挽救DBDPE诱导的斑马鱼跨代发育与视觉毒性","url":"https://pubmed.ncbi.nlm.nih.gov/42975500","doi":"10.1021/acs.est.6c09071","pmid":"42975500","journal":"Environ Sci Technol","kind":"paper","lang":"en","published_at":"2026-11-03T00:00:00+00:00","fetched_at":"2026-11-08T03:43:57+00:00","authors":["Zhang Y","Yang L","Xu T","Guo Y","Liu T","Hua J","Fu K","Li F","Gu J","Zhou Y","Han J","Zhou B"],"primary_topic":"repro-genetics","topics":[{"slug":"repro-genetics","score":5.0,"hits":["intergenerational","transgenerational"]},{"slug":"animal-models","score":3.2,"hits":["zebrafish"]},{"slug":"male","score":2.0,"hits":["sperm","testes"]},{"slug":"omics-methods","score":1.0,"hits":["transcriptome"]}],"topic_score":5.0,"preference_score":0.0,"preference_labels":[],"llm_score":72.0,"final_score":76.0,"score_dims":{"novelty":76,"rigor":78,"impact":62,"relevance":62,"translation":55},"recommend_reason":"该研究采用多剂量、双世代设计，并结合转录组和干预验证，较完整地刻画了父源环境暴露经精巢类固醇合成通路产生跨代毒性的机制，并提出孕前营养干预思路；但证据来自斑马鱼，对人ART的转化仍需谨慎。","keywords":["DBDPE","父源孕前暴露","跨代毒性","骨化三醇","精子质量","斑马鱼"],"selected":1,"story_id":149,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-gametes","source_name":"PubMed · 配子与性腺","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":"env-sci-tech","journal_tier":"field-top","journal_if":10.8,"is_mock":false,"summary_zh":"研究将雄性斑马鱼暴露于新型阻燃剂替代物DBDPE（十溴二苯乙烷）2个月，评估其对F1、F2代的跨代影响。结果显示，父源暴露损伤F0精子质量，并导致F2仔鱼畸形率升高；即使在低剂量下，F2仍出现明显眼部畸形，并伴随行为异常、视网膜变薄和光转导基因表达失调，提示视觉系统对跨代毒性高度敏感。转录组分析发现，类固醇生物合成通路和骨化三醇合成在F1至F2代中持续受扰，且F0精巢中骨化三醇水平明显不足；在暴露期间给父本补充骨化三醇，可恢复精子质量，并减轻子代视觉与发育毒性。结论提示，父源孕前营养干预可能降低新型污染物的跨代风险。","summary":"Growing evidence highlights the impact of preconception paternal environmental exposures on offspring health, yet the specific paternal contributions and transgenerational mechanisms of emerging contaminants remain poorly understood. Thus, we exposed male zebrafish to decabromodiphenyl ethane (DBDPE), a widely used replacement for legacy flame retardants, for 2 months to investigate its intergenerational (F1) and transgenerational (F2) effects. Paternal DBDPE exposure severely impaired sperm quality in F0 zebrafish, and induced transgenerational developmental toxicity with elevated malformations in F2 larvae. Moreover, significant eye malformations occurred even at low doses in F2 groups, revealing the visual system to be highly sensitive to transgenerational DBDPE toxicity. F1 and F2 larvae exhibited marked behavioral disorders, retinal thinning, and phototransduction gene dysregulation, indicating significant visual dysfunction. Notably, transcriptome analysis revealed that steroid biosynthesis (especially calcitriol synthesis) was consistently disrupted across dose levels and generations, with its enrichment factor progressively increasing from F1 to F2; this was accompanied by a pronounced deficiency of calcitriol in paternal F0 testes. Accordingly, paternal calcitriol supplementation during DBDPE exposure effectively restored F0 sperm quality and mitigated visual and developmental toxicity in offspring. These findings suggest that paternal exposure to emerging contaminants may induce intergenerational and transgenerational effects, and that targeted preconception nutritional intervention may reduce these risks.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}