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Our recent research found that excessive oxidative stress in ovaries of endometriosis patients induced senescence of cumulus granulosa cells. Here, we analyzed the transcriptomic and metabolomics profiles of follicles in a mouse model of endometriosis and in patients with endometriosis and investigated the potential function of changed metabolites in granulosa cells. RNA\u2010sequencing indicated that both endometriosis lesions and oxidative stress in mice induced abnormalities of reactive oxidative stress, steroid hormone biosynthesis, and lipid metabolism. The mouse model and women with endometriosis showed altered lipid metabolism. Nontargeted metabolite profiling of follicular fluid from endometriosis and male\u2010factor infertility patients by liquid chromatography mass spectrometry identified 55 upregulated and 67 downregulated metabolites. These differential metabolites were mainly involved in steroid hormone biosynthesis and glycerophospholipid metabolism. Phosphatidylinositol (PI 16:0\/18:2) was significantly elevated in follicular fluid from endometriosis patients compared with controls (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05), while lysophosphatidylinositol (LPI 18:2, 20:2, 18:1, 20:3 and 18:3) was reduced (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). Upregulated PI and downregulated LPI correlated with oocyte retrieval number and mature oocyte number. LPI inhibited cellular reactive oxidative stress induced by hemin in granulosa cells. Cell proliferation inhibition, senescence, and apoptosis induced by hemin were partially reversed by LPI. Moreover, LPI administration rescued hemin blocking of cumulus\u2010oocyte complex expansion and stimulated expression of ovulation\u2010related genes. Transcriptomic Switching mechanism at 5' end of the RNA transcript sequencing\u00a0and western blot revealed that LPI effects on granulosa cells were associated with its regulation of MAPK\u2010ERK1\/2 signaling, which was suppressed in the presence of hemin. In conclusion, our results revealed the dysregulation of lipid metabolism in endometriotic follicles. LPI may represent a novel agent for\n                    <jats:italic>in vitro<\/jats:italic>\n                    follicular culture that reverses the excessive oxidative stress from endometriotic lesions. \u00a9 2023 The Authors.\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.6079","type":"journal-article","created":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T01:00:09Z","timestamp":1680138009000},"page":"248-260","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Integrative analysis of transcriptomic and metabolomic profiles reveals abnormal phosphatidylinositol metabolism in follicles from endometriosis\u2010associated infertility 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