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To ensure the smooth progression of early embryo development, precise genomic regulation is crucial. Among the regulatory elements of genomic integrity, G-quadruplex (G4), as an important non-B-type DNA structure, is widely present in the genome and participates in gene expression regulation. However, the role of G4 structures in early embryonic development remain unclear. Here, we investigated the effect and mechanisms of G4 stabilization by G4 ligands, pyridostatin, and Braco-19, on early mouse embryonic development. Our results show that G4 ligands treatment-induced excessive G4 stabilization leads to disrupted DNA replication, and transcription\u2013replication conflicts contribute to elevated R-loop signals, causing an increase in double-strand breaks, thereby causing early embryo arrest. These findings highlight the critical role of DNA G4 structures in early embryo cleavage.<\/jats:p>","DOI":"10.1093\/reprod\/xaag057","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T11:26:20Z","timestamp":1777980380000},"source":"Crossref","is-referenced-by-count":0,"title":["G-Quadruplex stabilization impairs early embryo development by impairing DNA replication and inducing R-loops and DNA damage accumulation"],"prefix":"10.1093","volume":"171","author":[{"given":"Ke","family":"Xu","sequence":"first","affiliation":[{"name":"Guangzhou Key Laboratory of Metabolic Diseases and Reproductive Health, Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory, Reproductive Medicine Center, the Affiliated Guangdong Second Provincial General Hospital of Jinan University , Guangzhou, 510317,","place":["China"]},{"name":"Shenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology, The University of Hong Kong-Shenzhen Hospital , Guangdong,","place":["China"]},{"name":"Department of Obstetrics and Gynecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong , Hong Kong,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7451-9364","authenticated-orcid":false,"given":"Chao","family":"Li","sequence":"additional","affiliation":[{"name":"Guangzhou Key Laboratory of Metabolic Diseases and Reproductive Health, Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory, Reproductive Medicine Center, the Affiliated Guangdong Second Provincial General Hospital of Jinan University , Guangzhou, 510317,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youhui","family":"Lu","sequence":"additional","affiliation":[{"name":"Guangzhou Key Laboratory of Metabolic Diseases and Reproductive Health, Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory, Reproductive Medicine Center, the Affiliated Guangdong Second Provincial General Hospital of Jinan University , Guangzhou, 510317,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Litao","family":"Yi","sequence":"additional","affiliation":[{"name":"Guangzhou Key Laboratory of Metabolic Diseases and Reproductive Health, Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory, Reproductive Medicine Center, the Affiliated Guangdong Second Provincial General Hospital of Jinan University , Guangzhou, 510317,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0148-2414","authenticated-orcid":false,"given":"Qing-Yuan","family":"Sun","sequence":"additional","affiliation":[{"name":"Guangzhou Key Laboratory of Metabolic Diseases and Reproductive Health, Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory, Reproductive Medicine Center, the Affiliated Guangdong Second Provincial General Hospital of Jinan University , Guangzhou, 510317,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8069-0256","authenticated-orcid":false,"given":"Tie-Gang","family":"Meng","sequence":"additional","affiliation":[{"name":"Guangzhou Key Laboratory of Metabolic Diseases and Reproductive Health, Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory, Reproductive Medicine Center, the Affiliated Guangdong Second Provincial General Hospital of Jinan University , Guangzhou, 510317,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"key":"2026061017103559200_xaag057-B1","doi-asserted-by":"publisher","first-page":"1746","DOI":"10.1093\/nar\/gkw006","article-title":"Re-evaluation of G-quadruplex propensity with G4Hunter","volume":"44","author":"Bedrat","year":"2016","journal-title":"Nucleic Acids 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