{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:54:11Z","timestamp":1787032451073,"version":"build-2736575974"},"posted":{"date-parts":[[2026,4,26]]},"group-title":"Developmental Biology","reference-count":57,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T00:00:00Z","timestamp":1777161600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["R35GM141085"],"award-info":[{"award-number":["R35GM141085"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Folate-dependent one-carbon metabolism supplies methyl donors required for chromatin modification, yet how metabolic conditions shape epigenome establishment in the male germline remains poorly understood. Here, using a folate-deficient mouse model, we identify meiotic prophase I as a metabolically sensitive window in the male germline. By integrating in vivo germline analysis with bulk and single-cell transcriptomic and epigenomic profiling, we show that folate deficiency disturbs transcriptional programs in pachytene spermatocytes and preferentially perturbs CpG island (CGI)-associated promoters, which are characterized by bivalent H3K4me3 and H3K27me3 during meiosis. Consistent with this selective vulnerability, active chromatin marks, including H3K4me3 and H3K27ac, are markedly reduced at CGI-associated promoters under folate-deficient conditions. Notably, loci that later exhibit altered H3K4me3 enrichment in mature sperm show earlier chromatin perturbations during meiosis, suggesting that these sperm epigenomic alterations may originate during meiotic development. Together, these findings establish a mechanistic link between paternal folate deficiency and dynamic epigenomic remodeling of CGI-associated chromatin in the male germline.<\/jats:p>","DOI":"10.64898\/2026.04.22.720272","type":"posted-content","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T03:30:13Z","timestamp":1777260613000},"source":"Crossref","is-referenced-by-count":1,"title":["Paternal folate deficiency reveals meiosis as a metabolic sensing window in the male germline"],"prefix":"10.64898","author":[{"given":"Jasmine M.","family":"Esparza","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of California, Davis, Davis, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohan V.","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of California, Davis, Davis, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengwen","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of California, Davis, Davis, CA, USA"},{"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, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhisa","family":"Munakata","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of California, Davis, Davis, CA, USA"},{"name":"Department of Cell Science, Institute of Biomedical Sciences, School of Medicine, Fukushima Medical University, Fukushima, 960-1295 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saanvi","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of California, Davis, Davis, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Sakashita","sequence":"additional","affiliation":[{"name":"Laboratory for Developmental Genome Plasticity, RIKEN BioResource Research Center, Ibaraki, 305-0074, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So","family":"Maezawa","sequence":"additional","affiliation":[{"name":"Faculty of Science and Technology, Department of Applied Biological Science, Tokyo University of Science, Noda, Chiba, 281-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard M.","family":"Schultz","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of California, Davis, Davis, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1052-943X","authenticated-orcid":false,"given":"Satoshi H.","family":"Namekawa","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of California, Davis, Davis, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026042923152846000_2026.04.22.720272v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34295-5"},{"key":"2026042923152846000_2026.04.22.720272v1.2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.351569.124"},{"key":"2026042923152846000_2026.04.22.720272v1.3","first-page":"18","article-title":"Meiotic sex chromosome inactivation and the XY body: a phase separation hypothesis","volume":"79","year":"2021","journal-title":"Cell Mol Life Sci"},{"key":"2026042923152846000_2026.04.22.720272v1.4","doi-asserted-by":"crossref","unstructured":"Berger F (2024) Meiosis as a mechanism for epigenetic reprogramming and cellular rejuvenation. 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