{"id":12,"title":"The hidden threat: Integrated molecular mechanisms of lead-induced reproductive toxicity from endocrine disruption to epigenetic reprogramming","title_zh":"铅诱导生殖毒性的整合分子机制：从内分泌干扰到表观遗传重编程","url":"https://pubmed.ncbi.nlm.nih.gov/42981796","doi":"10.1016/j.jtemb.2026.127982","pmid":"42981796","journal":"J Trace Elem Med Biol","kind":"paper","lang":"en","published_at":"2026-10-30T00:00:00+00:00","fetched_at":"2026-11-08T03:43:49+00:00","authors":["Samaga R","Ranade SD","Rajora AD","Naresh P"],"primary_topic":"male","topics":[{"slug":"male","score":5.0,"hits":["leydig","sertoli","sperm","spermatogenesis","testis"]},{"slug":"oocyte","score":4.0,"hits":["follicular","oocyte quality","ovarian","ovarian reserve"]},{"slug":"repro-tox","score":4.0,"hits":["reproductive toxicity"]},{"slug":"repro-endo","score":2.0,"hits":["hypothalamic-pituitary-gonadal","ovulation"]},{"slug":"art-clinical","score":1.0,"hits":["subfertility"]},{"slug":"early-pregnancy","score":1.0,"hits":["pregnancy outcomes"]},{"slug":"contraception-health","score":1.0,"hits":["reproductive health"]},{"slug":"repro-aging","score":1.0,"hits":["mitochondrial dysfunction"]},{"slug":"omics-methods","score":1.0,"hits":["multi-omics"]}],"topic_score":5.0,"preference_score":15.0,"preference_labels":["多组学整合分析（任意生殖对象）","可转化到 ART 实验室的发现"],"llm_score":71.0,"final_score":86.0,"score_dims":{"novelty":60,"rigor":65,"impact":70,"relevance":85,"translation":60},"recommend_reason":"综述较全面地整合铅暴露的男女生殖毒性与表观遗传机制，适合环境暴露和生殖毒理参考；但非原始研究，人类证据有限，对ART实验室的直接转化价值中等。","keywords":["铅暴露","生殖毒性","氧化应激","表观遗传","多组学"],"selected":1,"story_id":278,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-embryo-omics","source_name":"PubMed · 胚胎/卵母细胞组学","source_tier":1,"mention_count":2,"has_interpretation":false,"journal_key":null,"journal_tier":"unknown","journal_if":null,"is_mock":false,"summary_zh":"该综述系统梳理铅（Pb²⁺）对男女生殖健康的毒性通路：干扰下丘脑-垂体-性腺/卵巢轴，诱发氧化应激、炎症、线粒体功能障碍、DNA损伤与凋亡，并损害精子发生、卵泡发育和卵母细胞质量；表观遗传改变可能造成持续性生殖功能障碍并影响后代。管理以减少暴露和临床螯合为主，抗氧化及微量营养素或起支持保护作用；但人类证据有限，多组学与生殖表型整合有望推动生物标志物发现和靶向干预。","summary":"Lead (Pb²⁺) is a persistent environmental toxicant that adversely affects male and female reproductive health through endocrine disruption, oxidative stress, inflammation, mitochondrial dysfunction, DNA damage, apoptosis, and epigenetic alterations. Pb²⁺ disrupts the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-ovarian axes while directly damaging reproductive cells. Excessive ROS generation, impaired antioxidant defense, and dysregulation of Nrf2 and NF-κB signaling promote oxidative and inflammatory injury, while mitochondrial dysfunction and impaired autophagy further accelerate cellular damage. In males, Pb²⁺ impairs Leydig and Sertoli cell function, steroidogenesis, blood-testis barrier integrity, spermatogenesis, sperm maturation, and fertilization, resulting in reduced sperm quality, motility, and DNA integrity. In females, Pb²⁺ disrupts ovarian steroidogenesis, follicular development, oocyte quality, and ovarian reserve, contributing to menstrual irregularities, impaired ovulation, subfertility, and adverse pregnancy outcomes. Epigenetic alterations may further contribute to persistent reproductive dysfunction and potentially affect offspring's health. Current management primarily involves exposure reduction and clinically indicated chelation, while antioxidant and micronutrient interventions may provide supportive protection. However, limitations in human evidence and incomplete understanding of molecular interactions remain important challenges. Integrating multi-omics approaches with reproductive phenotyping in the future may facilitate biomarker discovery and targeted therapy. Overall, Pb²⁺-induced reproductive toxicity is a multifactorial molecular disorder, emphasizing the need for early detection, preventive strategies, and targeted interventions to protect reproductive health.","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}}