Zhao Yan, Fernández-Montoro Andrea, Peeters Greet, Jatsenko Tatjana, De Coster Tine, Angel-Velez Daniel, Lefevre Thomas, Voet Thierry, Tšuiko Olga, Kurg Ants, Smits Katrien, Van Soom Ann, Vermeesch Joris Robert
Laboratory for Cytogenetics and Genome Research, Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium.
Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, 51010 Tartu, Estonia.
iScience. 2025 Apr 2;28(5):112337. doi: 10.1016/j.isci.2025.112337. eCollection 2025 May 16.
Whole-genome (WG) abnormalities, such as uniparental diploidy and triploidy, cause fetal death. Occasionally, they coexist with biparental diploid cells in live births. Understanding the origin and early development of WG abnormal blastomeres is crucial for explaining the formation of androgenotes, gynogenotes, triploidy, chimerism, and mixoploidy. By haplotyping 118 bovine blastomeres from the first cleavages, we identified that heterogoneic division occurs in both multipolar and bipolar cleaving zygotes. During heterogoneic division, parental genomes segregate into distinct blastomeres, resulting in the coexistence of uniparental and biparental diploid or polyploid cells. After culturing the totipotent blastomeres to three preimplantation stages and exploring transcriptomes of 446 cells, we discovered that stress responses contribute to developmental impairment in WG abnormal cells, resulting in either cell arrest or blastocyst formation. Their dominance in preimplantation embryos represents an overlooked cause of abnormal development. Haplotype-based screening could improve fertilization outcomes.
全基因组（WG）异常，如单亲二倍体和三倍体，会导致胎儿死亡。偶尔，它们会在活产中与双亲二倍体细胞共存。了解WG异常卵裂球的起源和早期发育对于解释雄核发育、雌核发育、三倍体、嵌合体和混倍体的形成至关重要。通过对首次卵裂产生的118个牛卵裂球进行单倍型分析，我们确定异源分裂发生在多极和双极分裂的合子中。在异源分裂过程中，亲代基因组分离到不同的卵裂球中，导致单亲二倍体和双亲二倍体或多倍体细胞共存。在将全能卵裂球培养到三个植入前阶段并探索446个细胞的转录组后，我们发现应激反应会导致WG异常细胞的发育受损，从而导致细胞停滞或囊胚形成。它们在植入前胚胎中的优势地位是发育异常的一个被忽视的原因。基于单倍型的筛选可以改善受精结果。
