{"doi":"10.1101/2020.07.24.220475","title":"Molecular Contribution to Embryonic Aneuploidy and Genotypic Complexity During Initial Cleavage Divisions of Mammalian Development","abstract":"ABSTRACT Embryonic aneuploidy is highly complex, often leading to developmental arrest, implantation failure, or spontaneous miscarriage in both natural and assisted reproduction. Despite our knowledge of mitotic mis-segregation in somatic cells, the molecular pathways regulating chromosome fidelity during the error-prone cleavage-stage of mammalian embryogenesis remain largely undefined. Using bovine embryos and live-cell fluorescent imaging, we observed frequent micro-/multi-nucleation of anaphase lagging or mis-segregated chromosomes in initial mitotic divisions that underwent unilateral inheritance, re-fused with the primary nucleus, or formed a chromatin bridge with neighboring cells. A correlation between a lack of maternal and paternal pronuclei fusion (syngamy), multipolar cytokinesis, and uniparental genome segregation was also revealed and single-cell DNA-seq showed propagation of primarily non-reciprocal mitotic errors in embryonic blastomeres. Depletion of the mitotic checkpoint protein, BUB1B/BUBR1, resulted in micro-/multi-nuclei formation, atypical cytokinesis, chaotic aneuploidy, and disruption of the kinase-substrate network regulating mitotic progression and exit, culminating in embryo arrest prior to genome activation. This demonstrates that embryonic micronuclei sustain multiple fates, provides a mechanism for blastomeres with uniparental origins, and substantiates the contribution of defective checkpoint signaling and/or the inheritance of other maternally-derived factors to the high genotypic complexity afflicting preimplantation development in higher-order mammals.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":123907,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.947,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":567530,"name":"Brittany L. Daughtry","orcid":"0000-0002-3526-6250","position":1,"is_corresponding":false},{"id":307550,"name":"Brett A. Davis","orcid":"0000-0001-7985-1921","position":2,"is_corresponding":false},{"id":567531,"name":"Melissa Y. Yan","orcid":"0000-0002-8079-7923","position":3,"is_corresponding":false},{"id":307548,"name":"Suzanne S. Fei","orcid":"0000-0002-9688-2890","position":4,"is_corresponding":false},{"id":51330,"name":"Lucia Carbone","orcid":"0000-0002-2118-107X","position":5,"is_corresponding":false},{"id":64732,"name":"Shawn L. Chavez","orcid":"0000-0002-8285-0222","position":6,"is_corresponding":false},{"id":64731,"name":"Kelsey E. Brooks","orcid":"0000-0003-3009-133X","position":0,"is_corresponding":true}],"reference_count":95,"raw_metadata":null,"created_at":"2026-07-18T23:15:03.403566Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}