极体活检验证胚胎母源异常CNV的减数分裂来源  

Application of polar body biopsy to verify the timing of embryonic maternal abnormal CNVs formation in meiosis

作　　者：董凤鸣 马慜悦 陆翀曌 张明 杨文豪 杨怡卓 穆莎 高原 董明理 彭红梅 DONG Feng-ming;MA Min-yue;LU Chong-zhao;ZHANG Ming;YANG Wen-hao;YANG Yi-zhuo;MU Sha;GAO Yuan;DONG Ming-li;PENG Hong-mei(Chinese PLA Medical School,Beijing 100039;Department of Obstetrics&Gynecology,the First Medical Center of Chinese PLA General Hospital,Beijing 100039)

机构地区：[1]中国人民解放军医学院,北京100039 [2]中国人民解放军总医院第一医学中心妇产科,北京100039

出　　处：《生殖医学杂志》2025年第4期525-532,共8页Journal of Reproductive Medicine

基　　金：国家重点研发计划资助(2022YFC2705305);军队计生专项科研课题(16JS011)。

摘　　要：目的研究胚胎母源染色体拷贝数变异(CNV)异常与卵母细胞第一次或第二次减数分裂的相关性。方法选择2023年5—10月在中国人民解放军总医院第一医学中心生殖医学中心行胚胎植入前遗传学非整倍体筛查(PGT-A)助孕的12对夫妇为研究对象,所有双原核(2PN)受精卵均活检第一极体、第二极体,并培养至囊胚期,对共计75枚囊胚活检行CNV检测;选取CNV异常胚胎行单核苷酸多态性(SNP)芯片检测进行父源、母源连锁分析;含母源异常CNV胚胎对应的第一、第二极体行CNV检测,验证胚胎异常CNV的减数分裂来源。结果共检测75枚囊胚,染色体存在异常的有39枚,共包含63处CNVs异常:其中整条染色体重复/缺失占比34.92%(22/63)、片段性重复/缺失异常占比20.63%(13/63)、染色体嵌合异常占比44.44%(28/63)。基于SNP芯片检测分析,63处异常CNVs中,母源CNVs占41.27%(26/63)、父源CNVs占31.75%(20/63)、无父母源倾向占14.29%(9/63)、6处异常CNVs判断结果为Unkown、另有2处暂时无法分析CNV异常来源。母源异常CNVs中有母源重复性CNVs 12处,其中减数分裂来源占比58.33%(7/12)、有丝分裂来源占比33.33%(4/12)、1处重复单体型为同源无法明确判断具体发生异常时期。囊胚和第一、第二极体的CNVs检测结果比对显示,两者异常CNVs减数分裂来源一致(7/7)。结论胚胎的重复型母源染色体异常多来自卵母细胞减数分裂阶段,第一次减数分裂阶段的错误更为常见。极体活检可验证生信算法分析胚胎的重复型母源染色体异常的有效性和准确性。Objective:To study the correlation between maternal copy number variations(CNVs)abnormalities of maternal origin in embryos and the first or second meiotic division in oocytes.Methods:The study recruited 12 couples who underwent preimplantation genetic testing for aneuploidy(PGT-A)for assisted reproduction at a reproductive medicine center of The First Medical Center of Chinese PLA General Hospital from May 2023 to October 2023.All bipolar nuclei(2PN)fertilized oocytes underwent biopsy of the first and second polar bodies and were cultured to the blastocyst stage.A total of 75 blastocysts were biopsied for CNV detection.CNV-abnormal embryos were selected for SNP microarray analysis to conduct paternal and maternal linkage analysis.The first and second polar bodies corresponding to the embryos with maternal CNV abnormalities were also tested for CNV to verify the meiotic origin of the embryonic CNV abnormalities.Results:A total of 75 blastocysts were tested,with 39 embryos showing chromosomal abnormalities,which included 63 abnormal CNVs segments.Among these,whole chromosome duplications/deletions accounted for 34.92%(22/63),segmental duplications/deletions for 20.63%(13/63),and chromosomal mosaicism abnormalities for 44.44%(28/63).Based on SNP chip analysis,among the 63 abnormal chromosomal CNVs,41.27%(26/63)were of maternal origin,31.75%(20/63)were of paternal origin,14.29%(9/63)were balanced,while 6 results were of unknown origin,and there were two others which origin of CNV anomalies couldn’t be analyzed temporarily.Among 12 repetitive CNVs of maternal origin,58.33%(7/12)were of meiotic origin and 33.33%(4/12)were of mitotic origin.For one of the repetitive haplotypes,the specific timing of the abnormality could not be determined due to homology(1/12).Based on the comparison of CNVs detection results between blastocysts and the first and the second polar bodies,the meiotic origin of the abnormal CNVs was consistent in both cases(7/7).Conclusions:The validation through polar body biopsy confirms that most of

关 键 词：胚胎植入前遗产学非整倍体筛查 异常染色体胚胎 非整倍体 极体 减数分裂 

分 类 号：R715.5[医药卫生—妇产科学]