{"id":394,"title":"DMRT1 is required at two steps of ovarian differentiation in rabbits","title_zh":"DMRT1参与兔卵巢分化的两个关键步骤","url":"https://pubmed.ncbi.nlm.nih.gov/42905833","doi":"10.1126/sciadv.aeh1087","pmid":"42905833","journal":"Sci Adv","kind":"paper","lang":"en","published_at":"2026-10-21T00:00:00+00:00","fetched_at":"2026-11-08T03:44:12+00:00","authors":["Dujardin E","Poulat F","Aura IB","Dewaele A","André M","McKey J","Le Gras S","Frambourg A","Jouneau L","Lupiáñez DG","Mandon-Pépin B","Pailhoux E"],"primary_topic":"oocyte","topics":[{"slug":"oocyte","score":8.0,"hits":["meiosis","meiotic","ovarian","ovaries","ovary"]},{"slug":"male","score":3.0,"hits":["testes","testicular","testis"]},{"slug":"art-clinical","score":1.0,"hits":["infertility"]},{"slug":"ivg-stem","score":1.0,"hits":["germ cells"]},{"slug":"ethics-policy","score":1.0,"hits":["regulation"]},{"slug":"omics-methods","score":1.0,"hits":["transcriptome"]}],"topic_score":8.0,"preference_score":0.0,"preference_labels":[],"llm_score":84.0,"final_score":92.0,"score_dims":{"novelty":88,"rigor":85,"impact":78,"relevance":82,"translation":72},"recommend_reason":"在兔模型中揭示DMRT1对卵巢分化的双重作用，补充了小鼠中缺失的表型，对性腺发育与女性生育力遗传机制有参考价值；但距ART临床直接应用尚远。","keywords":["DMRT1","卵巢分化","生殖细胞","减数分裂","兔模型","性腺发育"],"selected":1,"story_id":343,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-top-journals","source_name":"PubMed · CNS/大子刊/四大医学刊（生殖相关）","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":"sci-adv","journal_tier":"cns-sub","journal_if":11.7,"is_mock":false,"summary_zh":"该研究利用DMRT1突变兔模型，分析DMRT1缺失对卵巢分化的影响。早期性腺转录组显示，突变性腺具有区别于对照卵巢和睾丸的特异性表达谱；突变雌兔不育，DMRT1在生殖细胞中高表达至减数分裂启动，缺失后减数分裂关键基因下调，ChIP-seq证实DMRT1可直接结合这些基因。作者提出，DMRT1除决定睾丸分化外，还参与卵巢体细胞分化启动和生殖细胞分化两个步骤，并可能作为人类女性生育力相关基因。","summary":"The transcription factor Doublesex and Mab-3 Related Transcription Factor 1 (DMRT1) is essential for testis differentiation and male fertility, but less is known about its potential involvement in ovarian differentiation. In mice, Dmrt1-/- females are fertile, although they show a reduction of Stra8 expression. Using our DMRT1 mutant rabbit model, we analyzed ovarian differentiation when DMRT1 expression is abolished. First, we observed that during early gonadal development, DMRT1-/- gonads display a specific transcriptome different from control ovaries and control testes. Second, we assessed the infertility phenotype of mutant females. DMRT1 is highly expressed in germ cells until meiosis initiation, and its disruption leads to a down-regulation of key genes involved in the meiotic process. Chromatin immunoprecipitation sequencing data highlighted that DMRT1 can bind these genes in the rabbit ovary. Our study using the rabbit model shows that in addition to its role in testicular differentiation, DMRT1 has two important functions in ovarian differentiation: an initial involvement in the differentiation of somatic cells and a pivotal role in the differentiation of germ cells. Our data suggested that DMRT1 could be considered in human health as a gene necessary for female fertility.","interpretation_basis":null,"fulltext_status":"error","interpretation":null,"fulltext":{"available":false,"status":"error","reason":"抓取失败：HTTP 500 https://www.ebi.ac.uk/europepmc/webservices/rest/PMC13685955/fullTextXML","pmcid":"PMC13685955","license":null,"chars":0,"source":"Europe PMC","fetched_at":"2026-11-08T03:59:35+00:00"}}