It is widely held that the first two blastomeres of mammalian embryos are equally totipotent and that this totipotency belongs to the group of regulative properties. However, this interpretation neglects an important aspect: evidence only came from successful monozygotic twins which can speak only for those pairs of half-embryos that are able to regulate in the first place. Are the frequently occurring incomplete pairs simply an artefact, or do they represent a real difference, be it in the imperfect blastomere's ability to regulate growth or in the distribution of any compound X that constrains regulation? Using the model system of mouse embryos bisected at the 2-cell stage after fertilization, we present evidence that the interblastomere differences evade regulation by external factors and are already latent in oocytes. Specifically, an interblastomere imbalance of epiblast production persists under the most diverse culture conditions and applies to the same extent in parthenogenetic counterparts. As a result, cases in which twin blastocysts continued to develop in only one member account for 65 and 57% of zygotic and parthenogenetic pairs, respectively. The interblastomere imbalance is related to the subcellular distribution of gene products, as documented for the epiblast-related gene Cops3, using mRNA FISH in super-resolution mode confocal microscopy. Blastomere patterns of Cops3 mRNA distribution are α-amanitin-resistant. Thus, the imbalance originates not from de novo transcription, but from influences which are effective before fertilisation. These data expose previously unrecognized limits of regulative capacities of 2-cell stage blastomeres and point to aspects of cytoplasmic organization of the mouse oocyte that segregate unequally to blastomeres during cleavage.

中文翻译：

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2细胞小鼠胚胎中的卵裂球全能性差异是不对称mRNA分布介导的母体性状。

人们普遍认为，哺乳动物胚胎的前两个卵裂球具有同等的全能性，并且这种全能性属于调节特性组。但是，这种解释忽略了一个重要方面：证据仅来自成功的单卵双胞胎，这些卵双胞胎只能代表首先能够调节的那对半胚。频繁出现的不完整对仅仅是人工制品，还是代表真正的区别，是不完全的卵裂球调控生长的能力，还是限制调控的任何化合物X的分布？使用受精后在2细胞阶段一分为二的小鼠胚胎模型系统，我们目前提供的证据表明，卵裂球间差异逃避了外部因素的调控，并且已经潜伏在卵母细胞中。特别，在最多样化的培养条件下，成骨细胞间不平衡的成骨细胞持续存在，并且在孤雌生殖对应物中同样适用。结果，双胞胎囊胚仅在一个成员中继续发育的情况分别占合子和孤雌生殖对的65％和57％。如在表皮相关基因Cops3中所记载的那样，使用超分辨模式共聚焦显微镜观察mRNA的表达，间胚细胞不平衡与基因产物的亚细胞分布有关。Cops3 mRNA分布的卵裂球模式是耐α-amanitin。因此，失衡不是源于从头转录，而是源于受精前有效的影响。