{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T13:06:36Z","timestamp":1788872796473,"version":"build-2803163510"},"reference-count":75,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471792"],"award-info":[{"award-number":["82471792"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31770945"],"award-info":[{"award-number":["31770945"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFA0918400"],"award-info":[{"award-number":["2024YFA0918400"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Premature ovarian insufficiency (POI) is a major cause of infertility and endocrine dysfunction, in which chronic inflammation plays a critical role. The homeostasis of tissue\u2010resident macrophages and monocyte\u2010differentiated macrophages from peripheral blood serves as a key mechanism of inflammation across organs, yet their phenotypic plasticity in ovarian pathologies, including POI, remains poorly understood. Here, we identify that SIRT5 deficiency decreases macrophage count by attenuating monocyte\u2010macrophage differentiation. SIRT5 deficiency markedly attenuated follicular depletion and granulosa cell apoptosis, coinciding with reduced M1 macrophage infiltration and cytokine expression in the POI model. Mechanistically, we uncovered RAC2 as a novel succinylation substrate of SIRT5. SIRT5 deficiency elevated RAC2 succinylation, promoting its proteasomal degradation and thereby impairing CSF1R\u2010driven macrophage differentiation and M1 polarization. Pharmacological inhibition of SIRT5 recapitulated these protective effects, preserving follicular integrity and suppressing macrophage\u2010mediated inflammation. Our findings identify the SIRT5\u2013RAC2 axis as a key regulator of ovarian immune homeostasis and establish SIRT5 as a proof\u2010of\u2010concept therapeutic target for POI.<\/jats:p>","DOI":"10.1002\/advs.202518417","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T15:13:06Z","timestamp":1767798786000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["SIRT5\u2013RAC2 Axis Drives Monocyte\u2010to\u2010Macrophage Differentiation to Promote Inflammatory Injury in Premature Ovarian Insufficiency"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1754-9242","authenticated-orcid":false,"given":"Wenjing","family":"TanTai","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology National Key Laboratory of Immunity and Inflammation, Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology National Key Laboratory of Immunity and Inflammation, Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengnan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology of Changhai Hospital Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minjuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology National Key Laboratory of Immunity and Inflammation, Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixiao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology National Key Laboratory of Immunity and Inflammation, Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junfeng","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology National Key Laboratory of Immunity and Inflammation, Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology National Key Laboratory of Immunity and Inflammation, Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoding","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology National Key Laboratory of Immunity and Inflammation, Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology National Key Laboratory of Immunity and Inflammation, Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoqun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology National Key Laboratory of Immunity and Inflammation, Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology National Key Laboratory of Immunity and Inflammation, Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology National Key Laboratory of Immunity and Inflammation, Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitao","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology National Key Laboratory of Immunity and Inflammation, Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengfei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gynaecology and Obstetrics of the People's Hospital of Zhuji Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjuan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology of Changhai Hospital Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8489-6478","authenticated-orcid":false,"given":"Chaofeng","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology National Key Laboratory of Immunity and Inflammation, Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-024-00547-5"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2018.07.002"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2023-077469"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deae254"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1109122"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2010.06.008"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2019.154876"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmh011"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43032-022-01161-0"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.113513"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox14010039"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202048531"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-024-01021-w"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2019.09.011"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.11.013"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1207861"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2015.05.022"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.05.065"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2013.06.001"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2017.04.006"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-018-0819-z"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-024-01085-8"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.02.001"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2157-4"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adx0659"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btab711"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2024025680"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1007711"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11053-8"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2022.106566"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a021857"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-023-01575-y"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-023-03297-5"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-05859-0"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14122769"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmae020"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1703"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-023-00689-6"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1531246"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-082520-125411"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells14050330"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1089709"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2015.1009778"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-04-351817"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0171-9335(99)80058-2"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2014.142"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00972-z"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021909-135846"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2022.103491"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.681748"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2015.06.001"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-25837-3"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.1071"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2023.10.005"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2022.121339"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2016.142"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00461.2022"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.143.4.8754"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00657-10"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.232801"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.02.030"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2018.01.006"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5365.898"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-06150-y"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.124.012180"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2414734122"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2024.118865"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-023-00728-2"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-017-0739-3"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202302230R"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.11.102"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20111453"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/208103"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa203"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2021.101004"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202518417","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202518417","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202518417","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:07:11Z","timestamp":1788869231000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202518417"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,7]]},"references-count":75,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1002\/advs.202518417"],"URL":"https:\/\/doi.org\/10.1002\/advs.202518417","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,7]]},"assertion":[{"value":"2025-09-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e18417"}}