Key regulatory decisions during cleavage divisions in mammalian embryogenesis determine the fate of preimplantation embryonic cells. Single-cell RNA sequencing of early-stage—2-cell, 4-cell, and 8-cell—blastomeres show that the aryl hydrocarbon receptor (AHR), traditionally considered as an environmental sensor, directs blastomere differentiation. Disruption of AHR functions in Ahr knockout embryos or in embryos from dams exposed to dioxin, the prototypic xenobiotic AHR agonist, significantly impairs blastocyst formation, causing repression and loss of transcriptional heterogeneity of OCT4 and CDX2 and incidence of nonspecific downregulation of pluripotency. Trajectory—the path of differentiation—and gene variability analyses further confirm that deregulation of OCT4 functions and changes of transcriptional heterogeneity resulting from disruption of AHR functions restrict the emergence of differentiating blastomeres in 4-cell embryos. It appears that AHR directs the differentiation of progenitor blastomeres and that disruption of preimplantation AHR functions may significantly perturb embryogenesis leading to long-lasting conditions at the heart of disease in offspring’s adulthood.

哺乳动物胚胎发生中裂解分裂过程中的关键调控决策决定着床前胚胎细胞的命运。早期（2 细胞、4 细胞和 8 细胞）卵裂球的单细胞 RNA 测序表明，传统上被认为是环境传感器的芳基烃受体 (AHR) 可指导卵裂球分化。Ahr敲除胚胎或暴露于二恶英（原型异生 AHR 激动剂）的母体胚胎中 AHR 功能的破坏会显着损害囊胚形成，导致 OCT4 和 CDX2 转录异质性的抑制和丧失以及多能性非特异性下调的发生。轨迹（分化路径）和基因变异分析进一步证实，OCT4 功能的失调和 AHR 功能破坏导致的转录异质性变化限制了 4 细胞胚胎中分化卵裂球的出现。看来，AHR 指导着祖卵裂球的分化，并且植入前 AHR 功能的破坏可能会显着扰乱胚胎发生，导致后代成年后出现长期的核心疾病。