{"id":487,"title":"Interleukin-6 signaling disrupts blastocyst development and cell lineage composition in cattle","title_zh":"IL6R信号缺失损害牛囊胚发育并改变细胞谱系组成","url":"https://doi.org/10.1093/biolre/ioag248","doi":"10.1093/biolre/ioag248","pmid":null,"journal":"Biology of Reproduction","kind":"paper","lang":"en","published_at":"2026-11-03T00:00:00+00:00","fetched_at":"2026-11-08T03:44:35+00:00","authors":["Abigayle B Pollock","Hannah C O’Neill","Mary A Oliver","Jada L Nix","Fernando H Biase","Alan D Ealy"],"primary_topic":"early-embryo","topics":[{"slug":"early-embryo","score":8.0,"hits":["blastocyst","blastocysts","inner cell mass","trophectoderm","zygotes"]},{"slug":"animal-models","score":0.8,"hits":["bovine embryo"]}],"topic_score":8.0,"preference_score":0.0,"preference_labels":[],"llm_score":74.0,"final_score":74.0,"score_dims":{"novelty":70,"rigor":80,"impact":65,"relevance":78,"translation":52},"recommend_reason":"该研究通过基因编辑直接验证胚胎源IL6/IL6R信号在牛囊胚形成和ICM维持中的作用，对早期胚胎发育与胚胎免疫信号研究有参考价值；但属动物模型机制研究，与临床ART的直接转化距离较远。","keywords":["白细胞介素6","IL6R","牛胚胎","囊胚发育","内细胞团","胚胎多组学"],"selected":1,"story_id":117,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"crossref-core-journals","source_name":"Crossref · 核心期刊新上线","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":"biolreprod","journal_tier":"standard","journal_if":3.1,"is_mock":false,"summary_zh":"研究在牛受精卵中用电穿孔Cas9和两条靶向IL6R外显子2的sgRNA进行基因编辑，并于16细胞期通过靶向基因分型评估编辑效率。结果显示，IL6R缺失不影响卵裂和16细胞期发育，但降低第7、8天囊胚形成率；编辑囊胚的内细胞团（ICM）细胞数减少、滋养层（TE）细胞数不变、ICM:TE比例降低。结论提示胚胎来源IL6经IL6R/IL6ST复合物促进囊胚形成并维持ICM，但早期发育无缺陷，说明其他IL6家族细胞因子也参与牛胚胎前囊胚发育。","summary":"Abstract The bovine embryo expresses interleukin-6 (IL6) as well as its receptor system, which includes the ligand-binding IL6 receptor subunit (IL6R) and the common IL6 family signal-transducing component (IL6ST). Our laboratory recently determined that IL6ST activity facilitates normal in vitro embryo development and proper inner cell mass (ICM) size and morphology. We therefore hypothesized that embryo-derived IL6, acting through the IL6R–IL6ST receptor complex, drives these developmental outcomes. To test this, two single guide RNAs (sgRNAs) targeting exon 2 of IL6R were designed and electroporated with Cas9 protein into bovine zygotes. Editing efficiency was assessed in 16-cell embryos through targeted IL6R genotyping. Disruption of IL6R did not alter cleavage or development to the 16-cell stage but reduced blastocyst formation on days 7 and 8. The IL6R-edited blastocysts that were generated had reduced ICM cell numbers, no changes in trophectoderm (TE) cell number, and a reduced ICM:TE ratio. In summary, loss of IL6R signaling compromises blastocyst formation and alters cellular composition by reducing ICM cell numbers, thus supporting an embryotrophic role for embryo-derived IL6 acting through the IL6R/IL6ST complex. However, the absence of earlier developmental defects, which occurred in our prior IL6ST-targeting studies, suggests that additional embryo-derived IL6-family cytokines likely also contribute to pre-blastulation development in cattle.","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}}