Temporal and spatial aspects of fragmentation in early human embryos: possible effects on developmental competence and association with the differential elimination of regulatory proteins from polarized domains
Temporal and spatial aspects of fragmentation in early human embryos: possible effects on developmental competence and association with the differential elimination of regulatory proteins from polarized domains
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DOI：
10.1093/humrep/14.2.429
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发表时间：
1999-02-01
影响因子：
6.1
通讯作者：
Van Blerkom, J
中科院分区：
文献类型：
--
作者：
Antczak, M;Van Blerkom, J
本研究检查了体外受精获得的培养人胚胎中卵裂球断裂与断裂对以下8种调节蛋白分布的影响之间的关系，发现这些调节蛋白：（i）位于成熟卵母细胞质膜下的极化结构域中;（ii）卵裂球在卵裂过程中不平等地遗传：瘦素、信号转导和转录激活因子3（STAT 3）、Bar、Bcl-x、转化生长因子β 2（TGF β 2）、血管内皮生长因子（VEGF）、c-kit和表皮生长因子R（EGF-R）。每种类型的碎裂对受影响的卵裂球和胚胎发育能力的影响的严重程度似乎是与每种情况中涉及的特定碎裂模式相关的独特时间和空间特征的函数。研究结果表明，某些碎片模式可能导致特定卵裂球中8种调节蛋白的部分或几乎全部丢失，如果发生在1-或2-细胞阶段，受影响胚胎的发育潜力可能会受到特别的损害。相反，来自受精卵或2细胞胚胎中不含蛋白质结构域的卵裂球的部分的片段化，或在4细胞阶段之后通过含有调节蛋白结构域的卵裂球的片段化的完全损失不一定排除继续发育成胚泡，尽管胚胎的正常性和发育潜力可能受到损害。用膜磷脂酰丝氨酸Annexin V染色和卵裂球DNA原位末端标记（TUNEL）分析，结果表明胚胎碎片化与凋亡之间无直接关系。然而，虽然我们认为，细胞生理学的变化无关的凋亡是更可能的原因碎片，我们不能排除的可能性，碎片本身可能是一个启动程序的凋亡，如果临界比率或水平的发育重要的蛋白质被改变的部分或完全消除其极化域。研究结果进行了讨论，在人类卵母细胞和植入前阶段的胚胎中的调节蛋白极化的可能的发育意义。
This study examined the relationship between blastomere fragmentation in cultured human embryos obtained by in-vitro fertilization and the effect of fragmentation on the distribution of the following eight regulatory proteins found to be: (i) localized in the mature oocyte in subplasmalemmal, polarized domains; and (ii) unequally inherited by the blastomeres during cleavage: leptin, signal transducer and activator of transcription 3 (STAT3), Bar, Bcl-x, transforming growth factor beta 2 (TGF beta 2), vascular endothelial growth factor (VEGF), c-kit and epidermal growth factor R (EGF-R), Four basic patterns of fragmentation were observed. The severity of the impact of each type of fragmentation on the affected blastomere(s) and the developmental competence of the embryo appeared to be a function of the unique temporal and spatial features associated with the particular fragmentation pattern(s) involved in each instance. The findings demonstrate that certain patterns of fragmentation can result in the partial or near total loss of the eight regulatory proteins from specific blastomeres and that the developmental potential of the affected embryo can be particularly compromised if it occurs during the 1- or 2-cell stages. In contrast, fragmentation from portions of a fertilized egg or a blastomere(s) in a 2-cell embryo that do not contain the protein domains, or the complete loss by fragmentation of a regulatory protein domain-containing blastomere after the 4-cell stage does not necessarily preclude continued development to the blastocyst, although the normality and developmental potential of the embryo may be compromised. The possible association between fragmentation and apoptosis was examined by annexin V staining of plasma membrane phosphatidylserine and TUNEL analysis of blastomere DNA, No direct correlation between fragmentation and apoptosis was found following the analyses of fragmented embryos with these two markers. However, while we suggest that changes in cell physiology unrelated to apoptosis are the more likely causes of fragmentation, we cannot exclude the possibility that fragmentation itself may be an initiator of apoptosis if critical ratios or levels of developmentally important proteins are altered by partial or complete elimination of their polarized domains. The findings are discussed with respect to the possible developmental significance of regulatory protein polarization in human oocytes and preimplantation stage embryos.