{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T01:49:15Z","timestamp":1791856155736,"version":"4.3.4"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Primary dysmenorrhea (PD) is a prevalent gynecological disorder characterized by severe menstrual pain. Although excessive prostaglandin activity is a recognized driver of uterine hypercontractility, the molecular mechanisms linking prostaglandin imbalance to nitric oxide (NO) deficiency, coagulation abnormalities, and impaired uterine microcirculation remain incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A PD model was established in 12 female Sprague\u2013Dawley rats (control, n = 6; PD, n = 6) using estradiol valerate, repeated cold exposure, and oxytocin stimulation. Behavioral testing, biochemical and hormonal assays, histopathological evaluation, coagulation analysis, uterine microcirculation assessment, integrated transcriptomic and proteomic analyses, and targeted measurement of arginine and proline were performed to characterize PD-associated alterations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PD rats exhibited marked hyperalgesia, uterine hypercontractility, and reduced uterine blood perfusion. These changes were accompanied by significantly elevated uterine PGF\n                      <jats:sub>2<\/jats:sub>\n                      \u03b1 and PGE\n                      <jats:sub>2<\/jats:sub>\n                      levels, together with an increased PGF\n                      <jats:sub>2<\/jats:sub>\n                      \u03b1\/PGE\n                      <jats:sub>2<\/jats:sub>\n                      ratio (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.01), indicating a shift toward a contractile and vasoconstrictive prostaglandin profile. PD rats also showed decreased plasma NO and \u03b2-endorphin (\u03b2-EP) levels, altered estradiol (E\n                      <jats:sub>2<\/jats:sub>\n                      ) and progesterone (P) levels, uterine histopathological injury, and coagulation disturbance, consistent with impaired vascular regulation and endogenous analgesic capacity. Integrated transcriptomic and proteomic analyses revealed widespread molecular dysregulation in PD, with arginine and proline metabolism identified as the only pathway significantly enriched at both levels. Consistently, targeted measurement confirmed elevated uterine arginine and proline levels, suggesting a potential impairment in arginine utilization that may contribute to reduced NO bioavailability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings support a systems-level model in which prostaglandin imbalance, coagulation-associated microcirculatory dysfunction, and dysregulated arginine\u2013proline metabolism may jointly contribute to uterine ischemia and pain sensitization in PD. Our study proposes a refined molecular framework for PD pathogenesis and highlights the arginine\u2013NO axis as a potential therapeutic target tworthy of future investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1833346","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T04:26:48Z","timestamp":1778473608000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Integrated transcriptomic and proteomic profiling implicates prostaglandin\u2013nitric oxide network dysregulation in uterine microcirculatory impairment in primary dysmenorrhea"],"prefix":"10.3389","volume":"17","author":[{"given":"Yufei","family":"Li","sequence":"first","affiliation":[{"name":"School of Pharmacy, Shandong University of Traditional Chinese Medicine (TCM)","place":["Jinan, China"]},{"name":"Department of Anesthesiology, the First Affiliated Hospital of Shandong First Medical 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