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While germ cells have traditionally been considered the primary source of these mutations, increasing evidence suggests that a substantial fraction arise after fertilization. Here, we investigated the role of maternal DNA repair in shaping mutagenesis during this critical window by using a mouse model with oocyte-specific disruption of the homologous recombination factor RAD51 and a combination of cellular and molecular analyses. Loss of maternal RAD51 led to the accumulation of DNA double-strand breaks in oocytes without impairing their growth, meiotic maturation, or fertilization competence. In contrast, embryos derived from RAD51-deficient oocytes exhibited increased DNA damage and developmental delay during early cleavage stages. Whole-genome sequencing revealed a significant increase in de novo variants in offspring, the majority displaying intermediate allele frequencies consistent with post-zygotic mosaic mutations. These findings confirm that maternal DNA repair safeguards genome stability across the oocyte-to-embryo transition and identify early embryogenesis as a major source of de novo mutations, with implications for reproductive biology and the origins of genetic diseases.<\/jats:p>","DOI":"10.1093\/molehr\/gaag050","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:34:22Z","timestamp":1788449662000},"source":"Crossref","is-referenced-by-count":0,"title":["Maternal DNA repair safeguards genome stability during the oocyte-to-embryo transition"],"prefix":"10.1093","volume":"32","author":[{"given":"Mateus P","family":"Grejo","sequence":"first","affiliation":[{"name":"Departamento de Gen\u00e9tica e Evolu\u00e7\u00e3o, Centro de Ci\u00eancias Biol\u00f3gicas e da Sa\u00fade, Universidade Federal de S\u00e3o Carlos , S\u00e3o Carlos,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Djaci","family":"Augusto Neto","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica e Evolu\u00e7\u00e3o, Centro de Ci\u00eancias Biol\u00f3gicas e da Sa\u00fade, Universidade Federal de S\u00e3o Carlos , S\u00e3o Carlos,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ang\u00e9lica C","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica e Evolu\u00e7\u00e3o, Centro de Ci\u00eancias Biol\u00f3gicas e da Sa\u00fade, Universidade Federal de S\u00e3o Carlos , S\u00e3o Carlos,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindomar O","family":"Alves","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica e Evolu\u00e7\u00e3o, Centro de Ci\u00eancias Biol\u00f3gicas e da Sa\u00fade, Universidade Federal de S\u00e3o Carlos , S\u00e3o Carlos,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina H","family":"Macabelli","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica e Evolu\u00e7\u00e3o, Centro de Ci\u00eancias Biol\u00f3gicas e da Sa\u00fade, Universidade Federal de S\u00e3o Carlos , S\u00e3o Carlos,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9rgio A G","family":"Pereira-J\u00fanior","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica e Evolu\u00e7\u00e3o, Centro de Ci\u00eancias Biol\u00f3gicas e da Sa\u00fade, Universidade Federal de S\u00e3o Carlos , S\u00e3o Carlos,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tain\u00e3 F","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Embrapa Pecu\u00e1ria Sudeste, Fazenda Canchim , S\u00e3o Carlos,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anand K","family":"Pandey","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica e Evolu\u00e7\u00e3o, Centro de Ci\u00eancias Biol\u00f3gicas e da Sa\u00fade, Universidade Federal de S\u00e3o Carlos , S\u00e3o Carlos,","place":["Brazil"]},{"name":"Department of Veterinary Gynaecology and Obstetrics, College of Veterinary Science, Lala Lajpat Rai University of Veterinary and Animal Sciences , Hisar,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suellen G B","family":"Clemente","sequence":"additional","affiliation":[{"name":"National Institute of Science and Technology for Dairy Production Chain (INCT-Leite), Universidade Estadual de Londrina , Londrina,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah N","family":"Yokomizo","sequence":"additional","affiliation":[{"name":"National Institute of Science and Technology for Dairy Production Chain (INCT-Leite), Universidade Estadual de Londrina , Londrina,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo M","family":"Seneda","sequence":"additional","affiliation":[{"name":"National Institute of Science and Technology for Dairy Production Chain (INCT-Leite), Universidade Estadual de Londrina , Londrina,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0831-5264","authenticated-orcid":false,"given":"Ricardo P","family":"Nociti","sequence":"additional","affiliation":[{"name":"Departamento de Medicina Veterin\u00e1ria, Faculdade de Zootecnia e Engenharia de Alimentos, Universidade de S\u00e3o Paulo , Pirassununga,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fl\u00e1vio V","family":"Meirelles","sequence":"additional","affiliation":[{"name":"Departamento de Medicina Veterin\u00e1ria, Faculdade de Zootecnia e Engenharia de Alimentos, Universidade de S\u00e3o Paulo , Pirassununga,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick F","family":"Chinnery","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge , Cambridge,","place":["UK"]},{"name":"Medical Research Council Mitochondrial Biology Unit, University of Cambridge , Cambridge,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo A P","family":"Martins","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro , Rio de Janeiro,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre-Olivier","family":"Frappart","sequence":"additional","affiliation":[{"name":"Institute of Toxicology, University Medical Centre of the Johannes Gutenberg, Universit\u00e4t Mainz , 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