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Despite the widespread reporting of single-metabolic characteristics of postpartum IO, a comprehensive metabolic profile is lacking. Liquid chromatography\u2013tandem mass spectrometry was used to compare the metabolic changes in the serum, follicular fluid (FF), and ovarian tissue of six multiparous Holstein cows from each of the IO and healthy control (HC) groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Cows with IO had a higher milk yield during the previous lactation, poorer BCS, smaller largest follicle (LF) diameter at 63\u2009\u00b1\u20093 days in milk, and slower LF growth rate than HC cows (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01). They also exhibited higher serum levels of non-esterified fatty acids and aspartate aminotransferase and lower levels of estradiol, progesterone, insulin-like growth factor 1, calcium, and phosphorus (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01). Under IO conditions, 40, 51, and 14 differential metabolites were identified in serum, FF, and ovarian tissues, respectively. 12-Methyltridecanoic acid was consistently upregulated in cows with IO compared to HC cows across all samples (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01). Metabolomic pathway analysis identified significant alterations in six, three, and two metabolic pathways related to IO in the serum, FF, and ovarian tissues, respectively, affecting amino acid, energy, carbohydrate, lipid, and nucleotide metabolism. Valine, leucine, and isoleucine biosynthesis showed significant changes (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) in all samples.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In summary, these metabolic changes in cows with IO reflect a complex response to metabolic, oxidative, and inflammatory stresses. Our study provides the most comprehensive metabolic profile for cows with postpartum IO.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12917-025-05153-5","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T14:51:16Z","timestamp":1767624676000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Comprehensive serum, follicular fluid, and ovarian tissue profiling reveals systemic metabolic alterations in high-yielding dairy cows with postpartum inactive ovaries"],"prefix":"10.1186","volume":"22","author":[{"given":"Yuxi","family":"Song","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejie","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunlong","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"issue":"7","key":"5153_CR1","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1136\/vr.121.7.149","volume":"121","author":"O Markusfeld","year":"1987","unstructured":"Markusfeld O. 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