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The NOD\u2010like receptor family pyrin domain\u2010containing 3 (NLRP3)\u2010mediated pyroptosis has been proposed as a possible mechanism in POI. This study investigates the therapeutic effect of \u03b1\u2010ketoglutarate (AKG) on ovarian reserve function in POI rats and further explores the potential molecular mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>POI rats are caused by administration of cyclophosphamide (CTX) to determine whether AKG has a protective effect. AKG treatment increases the ovarian index, maintains both serum hormone levels and follicle number, and improves the ovarian reserve function in POI rats, as evidence by increased the level of lactate and the expression of rate\u2010limiting enzymes of glycolysis in the ovaries, additionally reduced the expression of NLRP3, Gasdermin D (GSDMD), Caspase\u20101, Interleukin\u201018 (IL\u201018), and Interleukin\u20101 beta (IL\u20101\u03b2). In vitro, KGN cells are treated with LPS and nigericin to mimic pyroptosis, then treated with AKG and MCC950. AKG inhibits inflammatory and pyroptosis factors such as NLRP3, restores the glycolysis process in vitro, meanwhile inhibition of NLRP3 has the same effect.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>AKG ameliorates CTX\u2010induced POI by inhibiting NLRP3\u2010mediated pyroptosis, which provides a new therapeutic strategy and drug target for clinical POI patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mnfr.202300784","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T02:13:07Z","timestamp":1707271987000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["\u03b1\u2010Ketoglutarate Improves Ovarian Reserve Function in Primary Ovarian Insufficiency by Inhibiting NLRP3\u2010Mediated Pyroptosis of Granulosa Cells"],"prefix":"10.1002","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6733-4046","authenticated-orcid":false,"given":"Ke","family":"Liu","sequence":"first","affiliation":[{"name":"Institute of Clinical Anatomy &amp; 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