{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T18:37:07Z","timestamp":1788201427274,"version":"build-2803163510"},"reference-count":90,"publisher":"American Society for Clinical Investigation","issue":"17","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":47,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2023YFC2705400"],"award-info":[{"award-number":["2023YFC2705400"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["31872846,82371680,82471703,82271698,82301899,82502025,82502024"],"award-info":[{"award-number":["31872846,82371680,82471703,82271698,82301899,82502025,82502024"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Frontier Technologies R&D Program of Jiangsu Province","award":["BF2025626"],"award-info":[{"award-number":["BF2025626"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:p>\n                    Defective endometrial decidualization is one major cause of female infertility, yet the underlying mechanisms remain elusive. Here, we identified that protein arginine methyltransferase 5 (PRMT5), which was upregulated during decidualization and by progesterone stimulation, was markedly downregulated in the endometria of patients with recurrent implantation failure (RIF), along with a global reduction of symmetric dimethylarginine (SDMA). Uterine stroma-specific ablation of\n                    <jats:italic>Prmt5<\/jats:italic>\n                    in mice severely impaired decidualization, leading to infertility. A multiomics analysis in human endometrial stromal cells (EnSCs) revealed that PRMT5 promoted decidualization primarily by catalyzing SDMA at arginine 346 (R346) of the orphan nuclear receptor Nur77, which directs its proper chromatin occupancy. Targeting the PRMT5\/Nur77 methylation axis, we designed a peptide, Pep-Nur77\n                    <jats:sup>R346K<\/jats:sup>\n                    , which rescued the decidualization of multiple preclinical models: PRMT5-deficient human EnSCs, both genetic knockout (\n                    <jats:italic>\n                      Prmt5\n                      <jats:sup>d\/d<\/jats:sup>\n                    <\/jats:italic>\n                    ) and pharmacologically inhibited mouse models, and most importantly, primary RIF EnSCs. In a retrospective cohort of 114 participants, the correlated reductions of endometrial PRMT5\/Nur77-R346me2s were confirmed, which demonstrated robust predictive value for pregnancy outcome. Our work establishes the PRMT5\/Nur77 methylation axis as a key regulator of endometrial receptivity and highlights both a diagnostic biomarker and a peptide-based therapeutic potential for infertility.\n                  <\/jats:p>","DOI":"10.1172\/jci178862","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T17:01:13Z","timestamp":1784307673000},"source":"Crossref","is-referenced-by-count":0,"title":["Targeting the PRMT5\/Nur77 methylation axis enhances endometrial decidualization capacity and female fertility in preclinical models"],"prefix":"10.1172","volume":"136","author":[{"given":"Zhiwen","family":"Cao","sequence":"first","affiliation":[{"name":"Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, State Key Laboratory of Pharmaceutical Biotechnology, and"},{"name":"Center for Molecular Reproductive Medicine, Nanjing University, Nanjing, Jiangsu, 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