单细胞全基因组测序分析体外受精三原核胚胎染色体

Chromosome analysis of tripronuclear embryos after in vitro fertilization by single cell whole genome sequencing

目的应用单细胞全基因组测序分析体外受精(IVF)三原核(3PN)胚胎染色体。方法选择2019年9月—2020年12月在本中心行IVF助孕的患者,治疗周期中废弃的3PN受精卵发育为胚胎,应用单细胞全基因组测序分析3PN胚胎染色体及拷贝数变异(CNV)。结果对3PN受精卵发育的11枚胚胎进行染色体核型和CNV检测,染色体核型结果显示:胚胎整倍体率为18.18%(2/11),非整倍体率为81.82%(9/11),性染色体异常比率为36.4%(4/11),染色体核型异常包含三体和单体。CNV检测结果发现:2个胚胎未发现4 Mb以上染色体片段缺失及重复情况,其他胚胎染色体异常片段包含了“Langer-Giedion综合征”“染色体18p缺失综合征”“染色体Xp11.22-p11.23重复综合征”和“染色体Xq27.3-q28微重复综合征”,而且嵌合体核型比率高。结论3PN受精卵发育成为胚胎的过程中有部分存在自我修复现象,可形成正常的二倍体胚胎;但染色体核型异常胚胎染色体异常片段复杂,嵌合体核型比率高。

Objective Chromosomes of tripronuclear(3 PN) embryos after in vitro fertilization(IVF) were analyzed by single cell whole genome sequencing. Methods Patients who were suffered from IVF in our center from September 2019 to December 2020 were selected. The discarded 3 PN fertilized eggs were cultured and developed into embryos during the treatment cycle, and the chromosomes and copy number variation(CNV) of 3 PN embryos were analyzed by single cell whole genome sequencing. Results Chromosome karyotype and CNV of 11 embryos developed from 3 PN fertilized eggs were detected.The results showed that the rate of embryonic euploid and non-embryonic euploid were 18.18%(2/11) and 81.82%(9/11),respectively. The rate of sex chromosome abnormality was 36.4%(4/11), respectively. And chromosome karyotype abnormality were trisomy and monomer. The results of CNV detection showed that there was no deletion or duplication of chromosome fragments above 4 Mb in 2 embryos, and the abnormal chromosome fragments of other embryos were included ‘Langer-Giedion syndrome’, ‘chromosome 18 p deletion syndrome’, ‘chromosome Xp11.22-p11.23 duplication syndrome’ and ‘chromosome Xq27.3-q28 microduplication syndrome’. Moreover, the ratio of chimerism karyotype was high. Conclusion In the process of developing 3 PN fertilized eggs into embryos, some of them can self-repair and form normal diploid embryos.However, abnormal chromosome fragments of embryos with abnormal karyotype were complex, and the ratio of chimerism karyotype was high.