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We observed that estrildid finches naturally carry the gain\u2010of\u2010function FSHR p.Thr449Ala mutation found in humans, yet do not develop OHSS, thereby providing a novel and system to study aspects of OHSS prevention. Cross\u2010species single\u2010cell analysis revealed that macrophages, the most abundant immune cells in ovaries, play a pivotal role in OHSS progression. Macrophage depletion exacerbates the manifestations of OHSS in both birds and rats. Pharmacological activation of the G protein\u2010coupled receptor 183 (GPR183) in ovarian macrophages, significantly alleviates OHSS symptoms. Mechanistically, GPR183 activation in macrophages maintains ovarian immune homeostasis by downregulating inflammatory factors (Interleukin 1 alpha: IL1A, Interleukin 6: IL6, Interleukin 1 beta: IL1B) and upregulating immune regulators responsive to external stimuli (sphingomyelin phosphodiesterase acid like 3A:\n                    <jats:italic>Smpdl3a<\/jats:italic>\n                    , Macrophage\u2010expressed gene 1:\n                    <jats:italic>Mpeg1<\/jats:italic>\n                    , Epithelial stromal interaction 1:\n                    <jats:italic>Epsti1<\/jats:italic>\n                    , Unc\u201093 homolog B1:\n                    <jats:italic>Unc93b1<\/jats:italic>\n                    , Apolipoprotein B mRNA editing enzyme catalytic subunit 1:\u00a0\n                    <jats:italic>Apobec1<\/jats:italic>\n                    ). It markedly altered CD44 molecule (\n                    <jats:italic>CD44<\/jats:italic>\n                    )\/Syndecan\u20104 (\n                    <jats:italic>SDC4<\/jats:italic>\n                    ) \u2010mediated intercellular communication between macrophages and endothelial\/stromal cells, thereby modulating the ovarian microenvironment. This study identifies ovarian macrophages as a key therapeutic target for OHSS and proposes GPR183 as a novel receptor target for precision macrophage\u2010based interventions.\n                  <\/jats:p>","DOI":"10.1002\/advs.75523","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T19:56:47Z","timestamp":1778011007000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Natural Resistance to Ovarian Hyperstimulation Syndrome in Estrildid Finches Reveals Macrophage GPR183 as a Potential Therapeutic Target"],"prefix":"10.1002","volume":"13","author":[{"given":"Xiaofei","family":"Yan","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory for Biodiversity and Biotechnology College of Life Sciences Nanjing Normal University  Nanjing P. R. 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