Integrated transcriptomic and proteomic profiling implicates prostaglandin-nitric oxide network dysregulation in uterine microcirculatory impairment in primary dysmenorrhea.

Background: 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. Methods: A PD model was established in 12 female Sprague-Dawley 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. Results: PD rats exhibited marked hyperalgesia, uterine hypercontractility, and reduced uterine blood perfusion. These changes were accompanied by significantly elevated uterine PGF Conclusion: These findings support a systems-level model in which prostaglandin imbalance, coagulation-associated microcirculatory dysfunction, and dysregulated arginine-proline 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-NO axis as a potential therapeutic target tworthy of future investigation.