{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:33Z","timestamp":1787028573877,"version":"build-2736575974"},"reference-count":139,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Slovak Research and Development Agency","award":["APVV-22-0071"],"award-info":[{"award-number":["APVV-22-0071"]}]},{"name":"the Slovak Academy of Sciences Agency VEGA","award":["2\/0041\/23"],"award-info":[{"award-number":["2\/0041\/23"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The maintenance of gene integrity is important for all types of cells, but, in the case of early embryonic cells, it is absolutely essential. This is because it influences not only the further development of the embryo but also, in some respects, the offspring. The occurrence and incorrect repair of cellular abnormalities after DNA damage during this period are the primary causes of fetal developmental disorders. If DNA damage occurs in germ cells or the fertilized oocyte and the DNA lesions are not satisfactorily repaired, this can lead to the occurrence of chromosomal aberrations during early embryogenesis and eventually to genetic instability during embryonic development. This developmental ability is related to the level of the DNA damage. Therefore, examining the events related to DNA damage response at the sub-cellular levels is of the utmost importance. In this context, subcellular diagnostics of such events during the selection of embryos with the highest implantation potential applied in the practice of assisted human reproduction are key to successful outcomes. It is important to apply new relevant knowledge from basic research to clinical practice, as well as considering new technical possibilities or trends in this area. The aim of this review is to provide a general overview of the molecular events associated with DNA damage in the early embryo and to outline the possible use of this basic knowledge in assisted reproduction procedures.<\/jats:p>","DOI":"10.3390\/ijms262010031","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T11:57:42Z","timestamp":1760529462000},"page":"10031","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Consequences of DNA Damage in the Early Embryo Are Important for Practical Procedures in Assisted Reproduction"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1686-2145","authenticated-orcid":false,"given":"Vladim\u00edr","family":"Baran","sequence":"first","affiliation":[{"name":"Institute of Animal Physiology, Centre of Biosciences, Slovak Academy of Sciences, \u0160olt\u00e9sovej 4, 040 00 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0457-9120","authenticated-orcid":false,"given":"\u0160tefan","family":"\u010ciko\u0161","sequence":"additional","affiliation":[{"name":"Institute of Animal Physiology, Centre of Biosciences, Slovak Academy of Sciences, \u0160olt\u00e9sovej 4, 040 00 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3216-2058","authenticated-orcid":false,"given":"Du\u0161an","family":"Fabian","sequence":"additional","affiliation":[{"name":"Institute of Animal Physiology, Centre of Biosciences, Slovak Academy of Sciences, \u0160olt\u00e9sovej 4, 040 00 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.fmre.2022.08.011","article-title":"The physiological and pathological mechanisms of early embryonic development","volume":"2","author":"Mu","year":"2022","journal-title":"Fundam. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"dev176966","DOI":"10.1242\/dev.176966","article-title":"The molecular mechanisms mediating mammalian fertilization","volume":"146","author":"Bhakta","year":"2019","journal-title":"Development"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"102034","DOI":"10.1016\/j.gde.2023.102034","article-title":"Nucleosomes in mammalian sperm: Conveying paternal epigenetic inheritance or subject to reprogramming between generations","volume":"79","author":"Peters","year":"2023","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1126\/science.aar7462","article-title":"Dual-spindle formation in zygotes keeps parental genomes apart in early mammalian embryos","volume":"361","author":"Reichmann","year":"2018","journal-title":"Science"},{"key":"ref_5","first-page":"R931","article-title":"Spindle Assembly: Two Spindles for Two Genomes in a Mammalian zygote","volume":"28","author":"Jord","year":"2018","journal-title":"Curr. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.ceb.2019.03.014","article-title":"Spindle assembly and chromosome dynamics during oocyte meiosis","volume":"60","author":"Mullen","year":"2019","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Dunkley, S., Scheffler, K., and Mogessie, B. (2022). Cytoskeletal form and function in mammalian oocytes and zygotes. Curr. Opin. Cell Biol., 75.","DOI":"10.1016\/j.ceb.2022.02.007"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1093\/biolre\/ioab210","article-title":"Acentriolar spindle assembly in mammalian female meiosis and the consequences of its perturbations on human reproduction","volume":"106","author":"Blengini","year":"2022","journal-title":"Biol. Reprod."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1017\/S0967199499000696","article-title":"Control of duration of the first two mitoses in a mouse embryo","volume":"7","author":"Ciemerych","year":"1999","journal-title":"Zygote"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1083\/jcb.201607062","article-title":"Meiotic spindle assembly and chromosome segregation in oocytes","volume":"215","author":"Bennabi","year":"2016","journal-title":"J. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"eabn4935","DOI":"10.1126\/sciadv.abn4935","article-title":"A developmentally programmed splicing failure contributes to DNA damage response attenuation during mammalian zygotic genome activation","volume":"8","author":"Wyatt","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Anger, M., Radonova, L., Horakova, A., Sekach, D., and Charousova, M. (2021). Impact of Global Transcriptional Silencing on Cell Cycle Regulation and Chromosome Segregation in Early Mammalian Embryos. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22169073"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1006\/dbio.2001.0501","article-title":"Dynamic reprogamming of DNA methylation in the early mouse embryo","volume":"241","author":"Santos","year":"2002","journal-title":"Dev. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"103195","DOI":"10.1016\/j.dnarep.2021.103195","article-title":"Genome maintenance during embryogenesis","volume":"106","author":"Munisha","year":"2021","journal-title":"DNA Repair"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"dmab046","DOI":"10.1093\/humupd\/dmab046","article-title":"DNA damage in preomplantation embryos and gametes: Specification, clinical relevance and repair strategies","volume":"28","author":"Musson","year":"2022","journal-title":"Hum. Reprod. Update"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/s41580-018-0008-z","article-title":"Dynamics of the epigenetic landscape during the maternal-to-zygotic transition","volume":"19","author":"Reik","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Pailas, A., Niaka, K., Zorzompokou, C., and Marangos, P. (2022). DNA damage response in fully grown mammalian oocytes. Cells, 11.","DOI":"10.3390\/cells11050798"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"14026","DOI":"10.3390\/ijms131114026","article-title":"Types, Causes, Detection and Repair of DNA Fragmentation in Animal and Human Sperm Cells","volume":"13","author":"Roy","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2777","DOI":"10.1007\/s00018-018-2833-9","article-title":"The Capacity of Oocytes for DNA Repair","volume":"75","author":"Stringer","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Leem, J., Bai, G.Y., and Oh, J.S. (2022). The Capacity to Repair Sperm DNA Damage in Zygotes is Enhanced by Inhibiting WIP1 Activity. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.841327"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S1534-5807(03)00373-3","article-title":"Dynamics of global gene expression changes during mouse preimplantation development","volume":"6","author":"Hamatani","year":"2004","journal-title":"Dev. Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1038\/nrm3643","article-title":"Re-starting life: Fertilization and the transition from meiosis to mitosis","volume":"14","author":"Clift","year":"2013","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1016\/j.cell.2016.11.009","article-title":"A Surveillance mechanism ensure repair of DNA lesions during zygotic reprogramming","volume":"167","author":"Ladstatter","year":"2016","journal-title":"Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.devcel.2017.07.026","article-title":"Zygotic genome activation in vertebrates","volume":"42","author":"Jukam","year":"2017","journal-title":"Dev. Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3828","DOI":"10.4161\/15384101.2014.967066","article-title":"Regulation of zygotic genome activation and DNA damage checkpoint acquisition at the mid-blastula transition","volume":"13","author":"Zhang","year":"2014","journal-title":"Cell Cycle"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"R35","DOI":"10.1016\/j.cub.2003.12.022","article-title":"Embryonic cleavage cycles: How is a mouse like a fly?","volume":"14","author":"Stumpff","year":"2004","journal-title":"Curr. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1146\/annurev-genet-111212-133531","article-title":"From egg to gastrula: How the cell cycle is remodeled during the Drosophila mid-blastula transition","volume":"48","author":"Farrell","year":"2014","journal-title":"Annu. Rev. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Schindler-Johnson, M., and Petridou, N.I. (2024). Collective effects of cell cleavage Dynamics. Front. Cell Dev. Biol., 12.","DOI":"10.3389\/fcell.2024.1358971"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1002\/ar.22692","article-title":"Cell proliferation patterns in early zebrafish development","volume":"296","author":"Schnabel","year":"2013","journal-title":"Anat. Rec."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3834","DOI":"10.1242\/dev.102368","article-title":"New insights into the maternal to zygotic transition","volume":"141","author":"Langley","year":"2014","journal-title":"Development"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Balder, P., Jones, C., Coward, K., and Yeste, M. (2024). Sperm chromatin: Evaluation, epigenetic signatures and relevance for embryo development and assisted reproductive technology outcomes. Eur. J. Cell Biol., 103.","DOI":"10.1016\/j.ejcb.2024.151429"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1093\/humrep\/deq139","article-title":"The fate of the mosaic embryo: Chromosomal constitution and development of day 4, 5 and 8 human embryos","volume":"25","author":"Santos","year":"2010","journal-title":"Hum. Reprod."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1093\/humrep\/des362","article-title":"Microarray analysis reveals abnormal chromosomal complements in over 70% of 14 normally developing human embryos","volume":"28","author":"Mertzanidou","year":"2013","journal-title":"Hum. Reprod."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1095\/biolreprod.110.089334","article-title":"DNA damage-sensing kinases mediate the mouse 2-cell embryo\u2019s response to genotoxic stress","volume":"85","author":"Mu","year":"2011","journal-title":"Biol. Reprod."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.mrfmmm.2011.06.010","article-title":"In vivo repair of DNA damage induced by X-rays in the early stages of mouse fertilization, and the influence of maternal PARP1 ablation","volume":"714","author":"Pacchierotti","year":"2011","journal-title":"Mutat. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e2019183118","DOI":"10.1073\/pnas.2019183118","article-title":"The intra-S phase checkpoint directly regulates replication elongation to preserve the integrity of stalled replisomes","volume":"118","author":"Liu","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1038\/s41586-024-07841-y","article-title":"Embryonic genome instability upon DNA replication timing program emergence","volume":"633","author":"Tahahachi","year":"2024","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1017\/S0967199410000286","article-title":"DNA damage and repair in human oocyte and embryos: A review","volume":"18","author":"Menezo","year":"2010","journal-title":"Zygote"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"103780","DOI":"10.1016\/j.dnarep.2024.103780","article-title":"Genome organization and stability in mammalian pre-implantation development","volume":"144","author":"Xu","year":"2024","journal-title":"DNA Repair"},{"key":"ref_40","first-page":"2","article-title":"Regulation of the embryonic cell cycle during mammalian preimplantation development","volume":"120","author":"Palmer","year":"2016","journal-title":"Curr. Top. Dev. Biol."},{"key":"ref_41","first-page":"607","article-title":"The same, only differentDNA damage checkpoints and their reversal throughout the cell cycle","volume":"128","author":"ShaltielI","year":"2015","journal-title":"J. Cell Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"620","DOI":"10.2741\/1822","article-title":"Meiotic spindle, spindle checkpoint and embryonic aneuploidy","volume":"11","author":"Wang","year":"2016","journal-title":"Front. Biosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1530\/jrf.0.1170097","article-title":"Analysis of apoptosis in the preimplantation bovine embryo using TUNEL","volume":"117","author":"Byrne","year":"1999","journal-title":"J. Reprod. Fertil."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.cub.2012.03.063","article-title":"Oocytes progress beyond prophase in the presence DNA damage","volume":"22","author":"Marangos","year":"2012","journal-title":"Curr. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.4161\/cc.24311","article-title":"The effect of DNA double-strand breaks on mouse oocyte meiotic maturation","volume":"12","author":"Ma","year":"2013","journal-title":"Cell Cycle"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Baran, V., Duricek, T., Pisko, J., Drutovic, D., and Solc, P. (2022). Cleavage of Early Mouse Embryo with Damaged DNA. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23073516"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.ejogrb.2014.01.010","article-title":"DNA repair signalling pathway genes are overexpressed in poor-quality pre-implantation human embryos with complex aneuploidy","volume":"175","author":"Bazrgar","year":"2014","journal-title":"Eur. J. Obs. Gynecol. Reprod. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"176","DOI":"10.2164\/jandrol.04152","article-title":"DNA damage in bovine sperm does not block fertilization and early embryonic development but induces apoptosis after the first cleavages","volume":"27","author":"Fatehi","year":"2006","journal-title":"J. Androl."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Ford, E., Currie, C.E., Taylor, D.M., Erent, M., Marston, A.L., Hartshorne, G.M., and McAinsh, A.D. (2020). The First Mitotic Division of the Human Embryo Is Highly Error-Prone. bioRxiv, 1\u201313.","DOI":"10.1038\/s41467-022-34294-6"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2860","DOI":"10.1016\/j.cell.2021.04.013","article-title":"Parental Genome Unification Is Highly Error-Prone in Mammalian Embryos","volume":"184","author":"Cavazza","year":"2021","journal-title":"Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2988","DOI":"10.1016\/j.cell.2022.06.028","article-title":"Replication Stress Impairs Chromosome Segregation and Preimplantation Development in Human Embryos","volume":"185","author":"Palmerola","year":"2022","journal-title":"Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.semcdb.2017.12.006","article-title":"Mammalian zygotic genome activation","volume":"84","author":"Svoboda","year":"2018","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1093\/humrep\/15.2.402","article-title":"Comparison of in-vitro development of embryos originating from either conventional in-vitro fertilization or intracytoplasmic sperm injection","volume":"15","author":"Dumoulin","year":"2000","journal-title":"Hum. Reprod."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Pisko, J., Spirkova, A., Cikos, S., Olexikova, L., Kovarikova, V., Sefcikova, Z., and Fabian, D. (2021). Apoptotic cells in mouse blastocysts are eliminated by neighbouring blastomeres. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-88752-0"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.semcdb.2020.12.007","article-title":"Genome diversity and instability in human germ cells and preimplantation embryos","volume":"113","author":"Shukla","year":"2021","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.ajhg.2020.03.005","article-title":"Incidence, origin, and predictive model for the detection and clinical management of segmental aneuploidies in human embryos","volume":"106","author":"Girardi","year":"2020","journal-title":"Am. J. Hum. Genet."},{"key":"ref_57","first-page":"631","article-title":"Tolerance thresholds underlie responses to DNA damage during germline development","volume":"38","author":"Jansen","year":"2024","journal-title":"Genes Dev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"172ra21","DOI":"10.1126\/scitranslmed.3004925","article-title":"Impairment of BRCA1-related DNA double-strand break repair leads to ovarian aging in mice and humans","volume":"5","author":"Titus","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Oktay, K., Turan, V., Titus, S., Stobezki, R., Liu, L., and Oktay, K.B. (2015). BRCA mutations, DNA repair deficiency, and ovarian aging. Biol. Reprod., 93.","DOI":"10.1095\/biolreprod.115.132290"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Garcia-Rodriguez, A., Gosalvez, J., Agarwal, A., Roy, R., and Johnston, S. (2018). DNA damage and repair in human reproductive cells. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20010031"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1093\/humupd\/dmz043","article-title":"BRCA-related ATM-mediated DNA double strandbreak repair andovarianaging","volume":"26","author":"Turan","year":"2020","journal-title":"Hum. Reprod. Update"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"gaab071","DOI":"10.1093\/molehr\/gaab071","article-title":"DNA repair and response to sperm DNA damage in oocytes and embryos, and the potential consequences in ART: A systematic review","volume":"28","author":"Newman","year":"2022","journal-title":"Mol. Hum. Reprod."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"75","DOI":"10.4103\/aja.aja_19_17","article-title":"Sperm DNA damage has a negative effect on early embryonic development following in vitro fertilization","volume":"20","author":"Zheng","year":"2018","journal-title":"Asian J. Androl."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"eaaz7602","DOI":"10.1126\/sciadv.aaz7602","article-title":"Sperm DNA damage causes genomic instability in early embryonic development","volume":"6","author":"Middelkamp","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1080\/15384101.2015.1128592","article-title":"DNA damage response during mouse oocyte maturation","volume":"15","author":"Mayer","year":"2016","journal-title":"Cell Cycle"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.bbrc.2007.04.162","article-title":"Deficiency in response to DNA double-strand breaks in mouse early preimplantation embryos","volume":"358","author":"Yukawa","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_67","first-page":"305","article-title":"Gamma-H2A.X\u2013a novel biomarker for DNA double-strand breaks","volume":"22","author":"Kuo","year":"2008","journal-title":"In Vivo"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Xiao, J., Liu, Y., Li, Z., Zhou, Y., Lin, H., Wu, X., Chen, M., and Xioa, W. (2012). Effects of the insemination of hydrogen peroxide-treated epididymal mouse spermatozoa on H2AX repair and embryo development. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0038742"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1093\/toxsci\/kfs120","article-title":"The activation of DNA damage detection and repair responses in cleavage-stage rat embryos by adameged paternal genome","volume":"127","author":"Grenier","year":"2012","journal-title":"Toxicol. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3336","DOI":"10.4161\/cc.26327","article-title":"Laser microbeam-induced DNA damage inhibits cell division in early fertilized eggs and early embryos","volume":"12","author":"Wang","year":"2013","journal-title":"Cell Cycle"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1001\/jama.2021.4788","article-title":"Diagnosis and Management of Infertility: A Review","volume":"326","author":"Carson","year":"2021","journal-title":"JAMA"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1146\/annurev-genet-072820-033609","article-title":"Errors of the Egg: The Establishment and Progression of Human Aneuploidy Research in the Maternal Germline","volume":"56","author":"Gruhn","year":"2022","journal-title":"Annu. Rev. Genet."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/978-1-4939-7780-2_19","article-title":"Time-lapse imaging for the detection of chromosomal abnormalities in primate preimplantation embryos","volume":"1769","author":"Daughtry","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Rodrigues, M.A., Probst, C.E., Zayats, A., Davidson, B., Riedel, M., Li, Y., and Venkatachalam, V. (2021). The in vitro micronucleus assay using imaging f low cytometry and deep learning. NPJ Syst. Biol. Appl., 7.","DOI":"10.1038\/s41540-021-00179-5"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Kalsbeek, D., and Goldteyn, R.M. (2017). G2\/M-phase checkpoint adaptation and micronuclei formation as mechanisms that contribute to genomic instability in human cells. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18112344"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nature14493","article-title":"Chromothripsis from DNA damage in micronuclei","volume":"522","author":"Zhang","year":"2015","journal-title":"Nature"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.ejogrb.2024.08.039","article-title":"Micronuclei in 2-cell embryos show higher blastocyst formation rates on human embryonic development","volume":"302","author":"Yao","year":"2024","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1038\/ncomms2249","article-title":"Dynamic blastomerebehaviour reflects human embryo ploidy by the four-cell stage","volume":"3","author":"Chavez","year":"2012","journal-title":"Nat. Commun."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1101\/gr.239830.118","article-title":"Single-cell sequencing of primate preimplantation embryos reveals chromosome elimination via cellular fragmentation and blastomere exclusion","volume":"29","author":"Daughtry","year":"2019","journal-title":"Genome Res."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Budrewicz, J., and Chavez, S.L. (2024). Insights into embryonic chromosomal instability: Mechanisms of DNA elimination during mammalian preimplantation development. Front. Cell Dev. Biol., 12.","DOI":"10.3389\/fcell.2024.1344092"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Shibasaki, I., Sugiyama, H., Kamada, Y., Nagatomo, H., Ito, D., Wakayama, S., and Wakayama, M.O.T. (2025). Extracting and analyzing micronuclei from mousetwo-cell embryos fertilized with freeze-dried spermatozoa. Commun. Biol., 8.","DOI":"10.1038\/s42003-024-07358-0"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Mashiko, D., Ikeda, Z., Yao, T., Tokoro, M., Fukunaga, N., Asada, Y., and Yamagata, K. (2020). Chromosome segregation error during early cleavage in mouse pre-implantation embryo does not necessarily cause developmental failure after blastocyst stage. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-57817-x"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1111\/gtc.12925","article-title":"Chromosome counting in the mouse zygote using low-invasive super-resolution live-cell imaging","volume":"27","author":"Hatano","year":"2022","journal-title":"Genes Cells"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1073\/pnas.1517628112","article-title":"Micronucleus formation causes perpetual unilateral chromosome inheritance in mouse embryos","volume":"113","author":"Yamagata","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/nature10802","article-title":"DNA breaks and chromosome pulverization from errors in mitosis","volume":"482","author":"Crasta","year":"2012","journal-title":"Nature"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.ydbio.2005.11.001","article-title":"The fate of mosaic aneuploid embryos during mouse development","volume":"289","author":"Lightfoot","year":"2006","journal-title":"Dev. Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1093\/humupd\/dmr014","article-title":"Chromosomal mosaicism in human preimplantation embryos: A systematic review","volume":"17","author":"Mastenbroek","year":"2011","journal-title":"Hum. Reprod. Update"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2238","DOI":"10.1016\/j.ajhg.2021.11.002","article-title":"Mosaic Human Preimplantation Embryos and Their Developmental Potential in a Prospective, Non-Selection Clinical Trial","volume":"108","author":"Capalbo","year":"2021","journal-title":"Am. J. Hum. Genet."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Ribas-Maynou, J., Novo, S., Torres, T., Salas-Huetos, A., Rovira, S., Antich, M., and Yeste, M. (2022). Sperm DNA integrity does play a crucial role for embryo development after ICSI, notably when good-quality oocytes from young donors are used. Biol. Res., 55.","DOI":"10.1186\/s40659-022-00409-y"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/s00018-016-2358-z","article-title":"DNA repair mechanisms in embryonic stem cells","volume":"74","author":"Fu","year":"2017","journal-title":"Cell Mol. Life Sci."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Khokhlova, V., Fesenko, Z.S., Sopova, J.V., and Leonova, E.I. (2020). Features of DNA repair in thre early stages of mammalian embryonic development. Genes, 11.","DOI":"10.3390\/genes11101138"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/j.celrep.2018.10.019","article-title":"Two RNase H2 mutants with differential RNMP processing activity reveal a threshold of ribonucleotide tolerance for embryonic development","volume":"25","author":"Uehara","year":"2018","journal-title":"Cell Rep."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"11165","DOI":"10.1038\/ncomms11165","article-title":"Mouse model of chromosome mosaicism reveals lineage-specific depletion of aneuploid cells and normal developmental potential","volume":"7","author":"Bolton","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Ramos-Ibeas, P., Gimeno, I., Ca\u00f1\u00f3n-Beltr\u00e1n, K., Guti\u00e9rrez-Ad\u00e1n, A., Rizos, D., and G\u00f3mez, E. (2020). Senescence and apoptosis during in vitro embryo develpmen in abovine model. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.619902"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Yu, B., van Tol, H.T.A., Stout, T.A.E., and Roelen, B.A.J. (2021). Cellular Fragments in the Perivitelline Space Are Not a Predictor of Expanded Blastocyst Quality. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.616801"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s43043-024-00176-8","article-title":"Embryo response to aneuploidy through self-correction mechanism: A literature review","volume":"29","author":"Harzif","year":"2024","journal-title":"Middle East Fertil. Soc. J."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/j.fertnstert.2023.07.022","article-title":"Chromosomal, gestational, and neonatal outcomes of embryos classified as a mosaic by preimplantation genetic testing for aneuploidy","volume":"120","author":"Viotti","year":"2023","journal-title":"Fertil. Steril."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"59","DOI":"10.23736\/S2724-606X.23.05296-X","article-title":"How should the best human embryo in vitro be? Current and future challenges for embryo selection","volume":"76","author":"Cimadomo","year":"2024","journal-title":"Minerva Obstet. Gynecol."},{"key":"ref_99","first-page":"03068","article-title":"Making and Selecting the Best Embryo in In vitro Fertilization","volume":"55","author":"Santamaria","year":"2024","journal-title":"Arch. Med. Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1007\/s10815-024-03048-2","article-title":"Mechanism of chromosomal mosaicism in preimplantation embryos and its effect on embryo development","volume":"41","author":"Zhang","year":"2024","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/s41421-024-00719-3","article-title":"Human embryos harbor complex mosaicism with broad presence of aneuploid cells during early development","volume":"10","author":"Zhai","year":"2024","journal-title":"Cell Discov."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"hoaf013","DOI":"10.1093\/hropen\/hoaf013","article-title":"Biopsy vs comprehensive embryo\/blastocyst analysis: A closer look at embryonic chromosome evaluation","volume":"2025","author":"Xu","year":"2025","journal-title":"Hum. Reprod. Open."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"108648","DOI":"10.1016\/j.reprotox.2024.108648","article-title":"The role of DNA damage response in human embryonic stem cells exposed to atmospheric oxygen tension: Implications for embryo development and differentiation","volume":"128","author":"Zhou","year":"2024","journal-title":"Reprod. Toxicol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s43032-024-01714-5","article-title":"Perspective in the Mechanisms for Repairing Sperm DNA Damage","volume":"32","author":"Li","year":"2025","journal-title":"Reprod. Sci."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.fertnstert.2018.11.035","article-title":"Double-stranded spermDNA damage is a cause of delayin embryo development and can impair implantation rates","volume":"111","author":"Casanovas","year":"2019","journal-title":"Fertil. Steril."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.ydbio.2018.01.014","article-title":"A speculative outlook on embryonic aneuploidy: Can molecular pathways be involved?","volume":"447","author":"Tsuiko","year":"2019","journal-title":"Dev. Biol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1093\/humrep\/deae224","article-title":"Do sperm factors influence embryonic aneuploidy? Long live the oocyte","volume":"39","author":"Fouks","year":"2024","journal-title":"Hum. Reprod."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1","DOI":"10.21037\/arh.2019.02.02","article-title":"Molecular aspects of aneuploidy in preimplantation human embryos: A mini-review","volume":"3","author":"Stolakis","year":"2019","journal-title":"Ann. Res. Hosp."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e174483","DOI":"10.1172\/JCI174483","article-title":"Single-cell DNA sequencing reveals a high incidence of chromosomal abnormalities in human blastocysts","volume":"134","author":"Chavli","year":"2024","journal-title":"J. Clin. Investig."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/nrg3245","article-title":"Human aneuploidy: Mechanisms and new insights into an age-old problem","volume":"13","author":"Nagaoka","year":"2012","journal-title":"Nat. Rev. Genet."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"R63","DOI":"10.1530\/REP-17-0569","article-title":"Causes and consequences of chromosome segregation error in preimplantation embryos","volume":"155","author":"FitzHarris","year":"2018","journal-title":"Reproduction"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1002\/pd.5927","article-title":"Origins and mechanisms leading to aneuploidy in human eggs","volume":"41","author":"Wartosch","year":"2021","journal-title":"Prenat. Diagn."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41580-022-00517-3","article-title":"Aneuploidy in mammalian oocytes and the impact of maternal ageing","volume":"24","author":"Charalambous","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2273","DOI":"10.1016\/j.devcel.2021.07.022","article-title":"Distinct classes of lagging chromosome underpin age-related oocyte aneuploidy in mouse","volume":"56","author":"Mihajlovic","year":"2021","journal-title":"Dev. Cell"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e57227","DOI":"10.15252\/embr.202357227","article-title":"Spindle assembly checkpoint insensitivity allows meiosis-II despite chromosomal defects in aged eggs","volume":"24","author":"Mihajlovic","year":"2023","journal-title":"EMBO Rep."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"e22922","DOI":"10.1096\/fj.202300062R","article-title":"Kinetochore deterioration concommitant with centromere weakening during aging in mouse oocyte meiosis-I","volume":"37","author":"Yin","year":"2023","journal-title":"FASEB J."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.1093\/humrep\/dex286","article-title":"Genome stability of bovine in vivo-conceived cleavage-stage embryos is higher compared to in vitro-produced embryos","volume":"32","author":"Tsuiko","year":"2017","journal-title":"Hum. Reprod."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1530\/REP-20-0086","article-title":"Aneuploidy during the onset of mouse embryo development","volume":"160","author":"Pauerova","year":"2020","journal-title":"Reproduction"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1095\/biolreprod.109.077909","article-title":"Evidence that a defective spindle assembly checkpoint is not the primary cause of maternal age-associated aneuploidy in mouse eggs","volume":"81","author":"Duncan","year":"2009","journal-title":"Biol. Reprod."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s10577-014-9428-6","article-title":"The frequency of precocious segregation of sister chromatids in mouse female meiosis I is affected by genetic background","volume":"22","author":"Danylevska","year":"2014","journal-title":"Chromosome Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"321","DOI":"10.3109\/19396368.2015.1073406","article-title":"Mammalian pre-implantation chromosomal instability: Species comparison, evolutionary considerations, and pathological correlations","volume":"61","author":"Carbone","year":"2015","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1101\/gr.200527.115","article-title":"Zygotes segregate entire parental genomes in distinct blastomere lineages causing cleavage-stage chimerism and mixoploidy","volume":"26","author":"Destouni","year":"2016","journal-title":"Genome Res."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Hornak, M., Oracova, E., Hulinska, P., Urbankova, L., and Rubes, J. (2012). Aneuploidy detection in pigs using comparative genomic hybridization: From the oocytes to blastocysts. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0030335"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1038\/s41556-021-00660-7","article-title":"Depletion of aneuploid cells in human embryos and gastruloids","volume":"23","author":"Yang","year":"2021","journal-title":"Nat. Cell Biol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1016\/j.ajhg.2022.07.009","article-title":"On the reproductive capabilities of aneuploid human preimplantation embryos","volume":"109","author":"Capalbo","year":"2022","journal-title":"Am. J. Hum. Genet."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"dev200391","DOI":"10.1242\/dev.200391","article-title":"Absence of a robust mitotic timer mechanism in early preimplantation mouse embryos leads to chromosome instability","volume":"149","author":"Allais","year":"2022","journal-title":"Development"},{"key":"ref_127","first-page":"312","article-title":"Human embryos commonly form abnormal nuclei during development: A mechanism of DNA damage, embryonic aneuploidy, and developmental arrest","volume":"31","author":"Kort","year":"2016","journal-title":"Hum. Reprod."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.bbrc.2022.05.075","article-title":"Micronucleus formation during early cleavage division is a potential hallmark of preimplantation embryonic loss in cattle","volume":"617","author":"Yao","year":"2022","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1016\/j.cell.2013.11.040","article-title":"Genome analyses of single human oocytes","volume":"155","author":"Hou","year":"2013","journal-title":"Cell"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1126\/science.aav7321","article-title":"Chromosome errors in human eggs shape natural fertility over reproductive life span","volume":"365","author":"Gruhn","year":"2019","journal-title":"Science"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"108320","DOI":"10.1016\/j.mrrev.2020.108320","article-title":"Mechanisms of oocyte aneuploidy associated with advanced maternal age","volume":"785","author":"Mikwar","year":"2020","journal-title":"Mutat. Res. Rev."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"101378","DOI":"10.1016\/j.arr.2021.101378","article-title":"Mitochondria: Their relevance during oocyte ageing","volume":"70","author":"Haigis","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1126\/science.1229112","article-title":"Probing meiotic recombination and aneuploidy of single sperm cells by whole-genome sequencing","volume":"338","author":"Lu","year":"2012","journal-title":"Science"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/s41586-020-2347-0","article-title":"Insights into variation in meiosis from 31,228 human sperm genomes","volume":"583","author":"Bell","year":"2020","journal-title":"Nature"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1023\/B:JOBB.0000041773.20072.9e","article-title":"Development of mitochondrial gene replacement therapy","volume":"36","author":"Khan","year":"2004","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_136","first-page":"39","article-title":"CRISPR\/Cas9 and mitochondrial gene replacement therapy: Promising techniques and ethical considerations","volume":"5","author":"Fogleman","year":"2016","journal-title":"Am. J. Stem Cells"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.fertnstert.2018.10.036","article-title":"Mitochondria as a tool for oocyte rejuvenation","volume":"111","author":"Labarta","year":"2019","journal-title":"Fertil. Steril."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1530\/REP-20-0351","article-title":"Does supplementation with mitochondria improve oocyte competence? A systematic review","volume":"161","author":"Ferreira","year":"2021","journal-title":"Reproduction"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"dev198341","DOI":"10.1242\/dev.198341","article-title":"Molecular contribution to embryonic aneuploidy and karyotypic complexity ininitial cleavage divisions of mammalian development","volume":"149","author":"Brooks","year":"2022","journal-title":"Development"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/20\/10031\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T11:59:11Z","timestamp":1760529551000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/20\/10031"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,15]]},"references-count":139,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["ijms262010031"],"URL":"https:\/\/doi.org\/10.3390\/ijms262010031","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,15]]}}}