Graduate School of Biology-Oriented Science and Technology, Kindai University, Wakayama, 649-6493, Japan.
Research and Development Center, Fuso Pharmaceutical Industries, Ltd., Osaka, 536-8523, Japan.
Sci Rep. 2020 Jan 21;10(1):854. doi: 10.1038/s41598-020-57817-x.
In the pre-implantation embryo, aneuploidy resulting from chromosome segregation error is considered responsible for pregnancy loss. However, only a few studies have examined the relationship between chromosome segregation errors during early cleavage and development. Here, we evaluated this relationship by live-cell imaging using the histone H2B-mCherry probe and subsequent single blastocyst transfer using mouse embryos obtained by in vitro fertilization. We showed that some embryos exhibiting early chromosomal segregation error and formation of micronuclei retained their developmental potential; however, the error affected the blastocyst/arrest ratio. Further, single-cell sequencing after live-cell imaging revealed that all embryos exhibiting micronuclei formation during 1 mitosis showed aneuploidy at the 2-cell stage. These results suggest that early chromosome segregation error causing micronuclei formation affects ploidy and development to blastocyst but does not necessarily cause developmental failure after the blastocyst stage. Our result suggests the importance of the selection of embryos that have reached blastocysts.
在着床前胚胎中,染色体分离错误导致的非整倍体被认为是导致妊娠丢失的原因。然而,只有少数研究检查了早期卵裂和发育过程中染色体分离错误之间的关系。在这里,我们通过使用组蛋白 H2B-mCherry 探针进行活细胞成像,并随后使用体外受精获得的小鼠胚胎进行单个囊胚转移来评估这种关系。我们表明,一些表现出早期染色体分离错误和微核形成的胚胎保留了其发育潜能;然而,这种错误影响了囊胚/阻滞比。进一步的,活细胞成像后的单细胞测序显示,在 1 次有丝分裂中显示微核形成的所有胚胎在 2 细胞阶段都表现出非整倍体。这些结果表明,导致微核形成的早期染色体分离错误会影响倍性和囊胚发育,但不一定会导致囊胚阶段后发育失败。我们的结果表明,选择已经达到囊胚阶段的胚胎的重要性。