{"id":205,"title":"Single-Cell Insights Into Pathogenic Profile of Orchitis and SREBP2-Associated Cholesterol Dysregulation in Spermatogenic Failure","title_zh":"单细胞解析睾丸炎致病图谱及SREBP2相关胆固醇失调在生精失败中的作用","url":"https://pubmed.ncbi.nlm.nih.gov/42966894","doi":"10.1002/advs.78572","pmid":"42966894","journal":"Adv Sci (Weinh)","kind":"paper","lang":"en","published_at":"2026-10-31T00:00:00+00:00","fetched_at":"2026-11-08T03:43:57+00:00","authors":["Tang Y","Jiang Q","Liu Y","Zhang W","Cui L","Lu X","Zhuang Z","Cheng J","Gao S","Fang Y","Hong K","Qiao J","Wang X","Jiang H","Zhang Z","Guo J","Liu Q"],"primary_topic":"male","topics":[{"slug":"male","score":5.0,"hits":["male infertility","spermatogenesis","spermatogonia","testes","testicular"]},{"slug":"omics-methods","score":4.0,"hits":["single-cell"]},{"slug":"ivg-stem","score":2.0,"hits":["germ cell","germ cells"]},{"slug":"art-clinical","score":1.0,"hits":["infertility"]}],"topic_score":5.0,"preference_score":0.0,"preference_labels":[],"llm_score":82.0,"final_score":88.0,"score_dims":{"novelty":86,"rigor":84,"impact":80,"relevance":82,"translation":74},"recommend_reason":"该研究以人睾丸单细胞图谱揭示睾丸炎中免疫-代谢轴驱动生精失败的新机制，并在小鼠模型中验证SREBP2为可干预靶点，对男性不育机制研究和转化探索均有参考价值。","keywords":["睾丸炎","单细胞转录组","SREBP2","胆固醇代谢","生精失败","男性不育"],"selected":1,"story_id":251,"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":2,"has_interpretation":false,"journal_key":"adv-sci","journal_tier":"general-top","journal_if":14.3,"is_mock":false,"summary_zh":"该研究对睾丸炎患者与健康对照的睾丸组织开展单细胞转录组测序（66,147个细胞），并结合组织学验证，发现CD8+效应T细胞和炎性巨噬细胞浸润、生殖细胞丢失、未分化精原细胞周期阻滞及体细胞纤维化/凋亡；间质细胞呈SREBP2相关胆固醇合成增强。小鼠睾丸炎模型中抑制SREBP2可改善生精、减少脂质蓄积并缓解纤维化，提示免疫激活-SREBP2-胆固醇失衡轴驱动生精失败，为炎症相关男性不育提供潜在靶点。","summary":"Orchitis, a testicular inflammation often triggered by infection, is a major cause of male infertility due to disruption of the testicular immune microenvironment and progressive loss of germ cells. Currently, no effective or targeted therapies are available. Here, we profile 66,147 single-cell transcriptomes from testes of orchitis patients and healthy controls, complemented by histological validation. We observe profound remodeling of testicular cell composition, with marked infiltration of CD8+ effector T cells and inflammatory macrophages, accompanied by germ cell loss. Undifferentiated spermatogonia exhibit cell-cycle arrest, while somatic cell populations display fibrosis, apoptosis, and loss of homeostatic functions. Notably, interstitial cells show SREBP2- associated reprogramming of cholesterol metabolism, characterized by increased synthesis. Inhibition of SREBP2 in a mouse orchitis model improves spermatogenesis, reduces lipid accumulation, and alleviates fibrosis. These findings demonstrate that immune activation-induced SREBP2 upregulation drives cholesterol metabolic imbalance and spermatogenic failure in orchitis, offering potential therapeutic options for inflammation-associated male infertility.","interpretation_basis":null,"fulltext_status":"ok","interpretation":null,"fulltext":{"available":true,"status":"ok","reason":"已取得 Europe PMC OA 全文","pmcid":"PMC13723723","license":"","chars":29997,"source":"Europe PMC","fetched_at":"2026-11-08T04:17:55+00:00"}}