Micronucleus formation during early cleavage division is a potential hallmark of preimplantation embryonic loss in cattle
Micronucleus formation during early cleavage division is a potential hallmark of preimplantation embryonic loss in cattle
复制标题
早期卵裂分裂过程中微核的形成是牛植入前胚胎丢失的潜在标志
DOI：
10.1016/j.bbrc.2022.05.075
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发表时间：
2022
影响因子：
3.1
通讯作者：
Sugimura Satoshi
中科院分区：
文献类型：
--
作者：
Yao Tatsuma;Ueda Akane;Khurchabilig Atchalalt;Mashiko Daisuke;Tokoro Mikiko;Nagai Hiroki;Sho Tei;Matoba Satoko;Yamagata Kazuo;Sugimura Satoshi
在包括人类和牛在内的非啮齿类哺乳动物的辅助生殖技术（ART）衍生胚胎中，染色体分离错误极有可能在早期卵裂分裂期间发生，导致非整倍性，包括嵌合体。然而，在这些哺乳动物中，早期卵裂和随后的胚胎发育过程中染色体分离错误之间的关系尚未详细说明。在本研究中，我们开发了非侵入性的活细胞成像的染色体分离动力学使用组蛋白H2 B-mCherry mRNA探针在牛植入前胚胎。卵裂早期染色体分离错误影响囊胚形成。特别是，胚胎经历异常染色体分离（ACS）与多个或大的微核形成很少发育成囊胚。严重ACS胚胎细胞周期持续时间延长。将染色体分离的活细胞成像囊胚转移给10头奶牛后，6头怀孕，其中4头产下足月后代。有趣的是，其中两个来自ACS的囊胚。因此，早期卵裂过程中染色体分离错误伴微核形成可能是牛植入前胚胎发生的致命标志。该技术已显示出了解染色体分离错误与随后的胚胎发育之间的关系，以及为医疗和畜牧生产选择可行的ART衍生胚胎的潜力。
In assisted reproductive technology (ART)-derived embryos of non-rodent mammals, including humans and cattle, chromosome segregation errors are highly likely to occur during early cleavage division, resulting in aneuploidy, including mosaicism. However, the relationship between chromosomal segregation errors during early cleavage and subsequent embryonic development has not been detailed in these mammals. In the present study, we developed non-invasive live-cell imaging of chromosome segregation dynamics using a histone H2B-mCherry mRNA probe in bovine preimplantation embryos. Chromosome segregation errors in early cleavage affected blastocyst formation. Especially, embryos that underwent abnormal chromosome segregation (ACS) with multiple or large micronucleus formation rarely developed into blastocysts. Embryos with the severe ACS had prolonged cell cycle duration. After transfer of blastocysts with live-cell imaging of chromosome segregation to ten cows, six became pregnant and four of them gave full-term offspring. Interestingly, two of them were derived from blastocysts with ACS. Hence, chromosomal segregation errors with micronucleus formation during early cleavage can be a fatal hallmark of preimplantation embryogenesis in cattle. This technique has shown potential for understanding the relationship between chromosome segregation error and subsequent embryo development, and for selecting viable ART-derived embryos for medical and livestock production.