Interleukin-6 (IL6) was recently identified as an embryotrophic factor in bovine embryos, where it acts primarily to mediate inner cell mass (ICM) size. This work explored whether IL6 affects epiblast (EPI) and primitive endoderm (PE) development, the two embryonic lineages generated from the ICM after its formation. Nuclear markers for EPI (NANOG) and PE (GATA6) were used to differentiate the two cell types. Increases (P < 0.05) in total ICM cell numbers and PE cell numbers were detected in bovine blastocysts at day 8 and 9 post-fertilization after exposure to 100 ng/ml recombinant bovine IL6. Also, IL6 increased (P < 0.05) the number of undifferentiated ICM cells (cells containing both PE and EPI markers). The effects of IL6 on EPI cell numbers were inconsistent. Studies were also completed to explore the importance of Janus kinase 2 (JAK2)-dependent signaling in bovine PE cells. Definitive activation of STAT3, a downstream target for JAK2, was observed in PE cells. Also, pharmacological inhibition of JAK2 decreased (P < 0.05) PE cell numbers. To conclude, IL6 manipulates ICM development after EPI/PE cell fates are established. The PE cells are the target for IL6, where a JAK-dependent signal is used to regulate PE numbers.

中文翻译：

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白细胞介素6促进牛胚泡的原始内胚层发育

白细胞介素 6 (IL6) 最近被确定为牛胚胎中的胚胎营养因子，它主要作用于介导内细胞团 (ICM) 的大小。这项工作探讨了 IL6 是否影响外胚层 (EPI) 和原始内胚层 (PE) 发育，这两种胚胎谱系在 ICM 形成后产生。EPI (NANOG) 和 PE (GATA6) 的核标记用于区分这两种细胞类型。在暴露于 100 ng/ml 重组牛 IL6 后，在受精后第 8 天和第 9 天，在牛囊胚中检测到总 ICM 细胞数和 PE 细胞数增加 (P < 0.05)。此外，IL6 增加（P < 0.05）未分化 ICM 细胞（同时包含 PE 和 EPI 标记的细胞）的数量。IL6 对 EPI 细胞数的影响不一致。还完成了研究以探索 Janus 激酶 2 (JAK2) 依赖性信号在牛 PE 细胞中的重要性。在 PE 细胞中观察到 STAT3（JAK2 的下游靶标）的确定性激活。此外，JAK2 的药理抑制作用降低了（P < 0.05）PE 细胞数量。总而言之，IL6 在 EPI/PE 细胞命运确定后操纵 ICM 发育。PE 细胞是 IL6 的目标，其中 JAK 依赖性信号用于调节 PE 数量。