This work aimed at evaluating the toxic effects of in ovo exposure to phenobarbital (PB) and unveiling the mode of action by transcriptome analysis in the embryonic liver of a model avian species, chicken (Gallus gallus). Embryos were initially treated with saline or 1 μg PB /g egg at Hamburger Hamilton Stage (HHS) 1 (1st day), followed by 20 days of incubation to HHS 46. At 21st day, chicks that pipped successfully were euthanized and dissected for assessing the PB caused effects on phenotypes and the liver transcriptome in both genders. In the PB treatment group, a 7% attenuation in tarsus length was found in females. While no adverse phenotypic effect on the liver somatic index (LSI) was observed, PB caused significant changes in the expressions of 52 genes in males and 516 genes in females (False Discovery Rate < 0.2, p value < 0.05, and absolute fold change > 2). PB exposure modulated the genes primarily enriched in the biological pathways of the cancer, cardiac development, immune response, lipid metabolism, and skeletal development in both genders, and altered expressions of genes related to the cellular process and neural development in females. However, mRNA expressions of chicken xenobiotic receptor (CXR)-mediated CYP genes were not induced in the PB treatment groups, regardless of males and females. On the contrary, PB exposure repressed the mRNA expressions of CYP2AC2 in males and CYP2R1, CYP3A37, and CYP8B1 in females. Although transcription factors (TFs) including SREBF1 and COUP-TFII were predicted to be commonly activated in both genders, some TFs were activated in a gender-dependent manner, such as PPARa in males and BRCA1 and IRF9 in females. Taken together, our results provided an insight into the mode of action of PB on the chicken embryos.

这项工作旨在评估的毒性作用卵内暴露于苯巴比妥（PB），并在模型鸟类的胚胎肝经转录组分析揭幕作用方式，鸡（鸡内金）。最初在汉堡汉密尔顿阶段（HHS）1（第1天）用盐水或1μgPB / g鸡蛋处理胚胎，然后孵育20天至HHS46。在第21天，对成功取卵的小鸡进行安乐死并解剖以评估PB对男女的表型和肝转录组都有影响。在PB治疗组中，女性的架长度减少了7％。虽然未观察到对肝体指数（LSI）的不良表型影响，但PB引起了男性52个基因和女性516个基因表达的显着变化（假发现率<0.2，p值<0.05，且绝对倍数变化> 2）。PB暴露调节了两个性别中主要富集于癌症，心脏发育，免疫应答，脂质代谢和骨骼发育等生物学途径的基因，并且改变了与女性细胞过程和神经发育相关的基因表达。但是，无论男性和女性，PB处理组均未诱导鸡异种受体（CXR）介导的CYP基因的mRNA表达。相反，PB曝光压抑的mRNA表达CYP2AC2男性和CYP2R1，CYP3A37和CYP8B1在女性中。尽管包括SREBF1和COUP-TFII在内的转录因子（TFs）预计在两种性别中均被普遍激活，但某些TFs以性别依赖性方式被激活，例如雄性中的PPARa和雌性中的BRCA1和IRF9。两者合计，我们的结果提供了对PB在鸡胚上的作用方式的见解。