{"id":147,"title":"Plant-derived exosome-like nanovesicles alleviate testicular injury by suppressing p21-mediated cell cycle arrest in Sertoli cells","title_zh":"植物来源外泌体样纳米囊泡通过抑制p21介导的支持细胞周期阻滞缓解睾丸损伤","url":"https://pubmed.ncbi.nlm.nih.gov/42989243","doi":"10.1186/s12951-026-04871-8","pmid":"42989243","journal":"J Nanobiotechnology","kind":"paper","lang":"en","published_at":"2026-08-11T00:00:00+00:00","fetched_at":"2026-11-08T03:43:57+00:00","authors":["Xiao Y","Hou X","Wei C","Ding M","Tan W","Tu P","Zhang X","Jiang Y"],"primary_topic":"male","topics":[{"slug":"male","score":12.0,"hits":["azoospermia","male infertility","sertoli","sperm","testicular","testis"]},{"slug":"art-clinical","score":1.0,"hits":["infertility"]},{"slug":"omics-methods","score":1.0,"hits":["single-cell rna"]}],"topic_score":12.0,"preference_score":0.0,"preference_labels":[],"llm_score":77.0,"final_score":77.0,"score_dims":{"novelty":85,"rigor":72,"impact":72,"relevance":82,"translation":68},"recommend_reason":"跨物种植物纳米囊泡递送miRNA靶向p21修复支持细胞周期阻滞，机制新颖且有人类NOA单细胞数据佐证，为男性不育提供可转化的候选纳米疗法；但证据仍限于单一小鼠模型，剂量、安全性与长期效应信息有限。","keywords":["植物外泌体样纳米囊泡","支持细胞","p21/CDKN1A","miR-159b-3p","睾丸损伤","男性不育"],"selected":1,"story_id":447,"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":null,"journal_tier":"unknown","journal_if":null,"is_mock":false,"summary_zh":"本研究利用肉苁蓉来源的外泌体样纳米囊泡（CDELNs）治疗小鼠睾丸损伤。CDELNs经硫酸肝素蛋白多糖介导的内吞作用被睾丸支持细胞优先摄取，其携带的miR-159b-3p直接靶向Cdkn1a mRNA的3'UTR，下调p21，从而缓解p21介导的支持细胞周期阻滞。在睾丸损伤小鼠模型中，CDELNs改善了睾丸组织病理、恢复血睾屏障完整性、提升精子质量与关键激素水平并部分恢复生育力。对非梗阻性无精子症患者单细胞RNA测序数据的再分析显示支持细胞CDKN1A表达升高，提示该通路可能参与人类睾丸功能异常。","summary":"Testicular dysfunction represents a leading cause of male infertility, yet effective therapeutic interventions remain elusive. Here, we report a novel plant-derived nanotherapeutic strategy for testicular injury using Cistanche deserticola-derived exosome-like nanovesicles (CDELNs). CDELNs are preferentially internalized by testicular Sertoli cells via heparan sulfate proteoglycan (HSPG)-mediated endocytosis, whereupon, CDELN-derived miR-159b-3p directly targets the 3'UTR of Cdkn1a mRNA, leading to downregulation of p21 and subsequent alleviation of p21-mediated cell cycle arrest in Sertoli cells. In a mouse model of testicular injury, administration of CDELNs significantly ameliorated testicular histopathology, restored blood-testis barrier integrity, improved sperm quality and key hormone levels, and partially rescued fertility. Notably, reanalysis of publicly available single-cell RNA-seq data from non-obstructive azoospermia (NOA) patients revealed elevated CDKN1A expression in Sertoli cells, suggesting that p21 dysregulation may also contribute to human testicular dysfunction. In summary, our study supports CDELNs as a natural nanovesicle-based candidate that protects against testicular injury through miRNA-mediated p21 suppression, offering a promising translational avenue for male infertility.","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}}