Sturm K S, Flannery M L, Pedersen R A
Laboratory of Radiobiology and Environmental Health, University of California, San Francisco 94143-0750.
Dev Dyn. 1994 Sep;201(1):11-28. doi: 10.1002/aja.1002010103.
Parthenogetically activated, diploid mouse oocytes can develop to midgestation stages in utero. However, even these advanced parthenogenones appear to die because of much reduced trophoblast and yolk sac development. Previous studies have compared the general features of parthenogenetic and androgenetic development and determined the fate of uniparental cells in chimeras with normal embryos. These studies led to the concept of genomic imprinting as the cause for developmental failure when either the maternal or the paternal genome is duplicated, with the corresponding deficiency of the other. Genomic imprinting appears to arise during gametogenesis and to act through dosage effects in a set of imprinted genes, whose expression depends on their parental origin. In this study we undertook a more detailed morphological analysis of parthenogenetic development in the mouse and established a classification system to quantify the developmental extent of parthenogenones. We found that the failure of parthenogenones occurred at different times during early postimplantation development, generating a spectrum of concepti which had developed to different extents, with only a small fraction of the embryos reaching advanced somite stages. In all parthenogenones differentiation and proliferation of the trophectoderm and primitive endoderm lineages (both extraembryonic) was abnormal, and in all, even the best-developed parthenogenones, we observed similar deficiencies in the embryonic lineages, especially the mesoderm. Common to all abnormally developed lineages was that the proportion of undifferentiated precursor cells was much reduced, while their differentiated descendants were relatively abundant. We propose, therefore, that the failure of parthenogenones to develop to term is due to abnormal regulation of differentiation and proliferation in both embryonic and extraembryonic lineages. In this hypothesis, the apparent tissue specific defects observed in parthenogenones arise as a consequence of the functional importance of certain tissues (like the trophoblast) early in development. The spectrum of parthenogenones thus appears to reflect critical events in early development, whose regulation are affected by genomic imprinting.
孤雌生殖激活的二倍体小鼠卵母细胞可在子宫内发育至妊娠中期阶段。然而，即使是这些发育较成熟的孤雌生殖胚胎似乎也会死亡，原因是滋养层和卵黄囊发育明显受限。此前的研究比较了孤雌生殖和雄核发育的一般特征，并确定了单亲细胞在与正常胚胎嵌合体中的命运。这些研究引出了基因组印记的概念，即当母本或父本基因组被复制而另一方相应缺失时，发育失败的原因。基因组印记似乎在配子发生过程中产生，并通过一组印记基因的剂量效应起作用，这些基因的表达取决于其亲本来源。在本研究中，我们对小鼠孤雌生殖发育进行了更详细的形态学分析，并建立了一个分类系统来量化孤雌生殖胚胎的发育程度。我们发现，孤雌生殖胚胎的发育失败发生在着床后早期发育的不同时间点，产生了一系列发育程度不同的概念体，只有一小部分胚胎达到高级体节阶段。在所有孤雌生殖胚胎中，滋养外胚层和原始内胚层谱系（均为胚外谱系）的分化和增殖均异常，而且在所有胚胎中，即使是发育最好的孤雌生殖胚胎，我们也观察到胚胎谱系，尤其是中胚层存在类似的缺陷。所有异常发育谱系的共同之处在于，未分化前体细胞的比例大幅降低，而其分化后代相对丰富。因此，我们提出，孤雌生殖胚胎无法发育至足月是由于胚胎和胚外谱系中分化和增殖的异常调节。在这一假设中，孤雌生殖胚胎中观察到的明显组织特异性缺陷是某些组织（如滋养层）在发育早期功能重要性的结果。因此，孤雌生殖胚胎的谱系似乎反映了早期发育中的关键事件，其调节受到基因组印记的影响。
