Dynamic blastomere behaviour reflects human embryo ploidy by the four-cell stage.

Dynamic blastomere behaviour reflects human embryo ploidy by the four-cell stage.
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DOI:
10.1038/ncomms2249
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发表时间:
2012
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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先前的研究已经证明,人类胚胎中的非整倍体是令人惊讶的频繁,50-80%的卵裂期人类胚胎携带异常的染色体数目。在这里,我们结合联合收割机非侵入性的时间推移成像与核型重建的四细胞人类胚胎中的所有卵裂球,以解决这一假设,卵裂球的行为可能反映倍性在前两次卵裂分裂。我们证明,精确的细胞周期参数定时观察到在所有整倍体胚胎的四细胞阶段,而只有30%的非整倍体胚胎表现出正常的时间窗口内的参数值。此外,我们观察到人胚胎非整倍体的产生是复杂的,含有染色体的片段/微核经常出现,并可能持续存在或在间期被重吸收。这些发现表明,单个卵裂球的细胞周期和碎片参数是倍性的诊断,适合自动跟踪算法,并可能在减少易流产胚胎移植的临床相关性。 异常的人类胚胎发育与体外受精过程中观察到的胚胎停滞有关。Chavez和他的同事对人类胚胎进行了延时成像,发现染色体异常的胚胎表现出不同的细胞周期参数,这些参数可能有助于停滞。
Previous studies have demonstrated that aneuploidy in human embryos is surprisingly frequent with 50–80% of cleavage-stage human embryos carrying an abnormal chromosome number. Here we combine non-invasive time-lapse imaging with karyotypic reconstruction of all blastomeres in four-cell human embryos to address the hypothesis that blastomere behaviour may reflect ploidy during the first two cleavage divisions. We demonstrate that precise cell cycle parameter timing is observed in all euploid embryos to the four-cell stage, whereas only 30% of aneuploid embryos exhibit parameter values within normal timing windows. Further, we observe that the generation of human embryonic aneuploidy is complex with contribution from chromosome-containing fragments/micronuclei that frequently emerge and may persist or become reabsorbed during interphase. These findings suggest that cell cycle and fragmentation parameters of individual blastomeres are diagnostic of ploidy, amenable to automated tracking algorithms, and likely of clinical relevance in reducing transfer of embryos prone to miscarriage. Abnormal human embryo development is implicated in the embryo arrest observed during in vitro fertilization. Chavez and colleagues perform time-lapse imaging on human embryos and find that chromosomally abnormal embryos exhibit diverse cell cycle parameters that may contribute to arrest.
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