Aquaporin-9 and endometriomas: pathophysiological insights from a case-control study

Biomarkers. 2026 Feb;31(1):60-65. doi: 10.1080/1354750X.2026.2615799. Epub 2026 Jan 21.

Abstract

Introduction: Endometriosis is an estrogen-dependent condition characterized by ectopic implantation of endometrial tissue; molecular mechanisms underlying lesion persistence remain incompletely understood. Aquaporins (AQPs), transmembrane water channels involved in migration and proliferation, have been implicated in endometriosis pathophysiology, although data on AQP9 are limited.

Methods: This prospective case-control study evaluated AQP9 concentrations in serum, peritoneal fluid, and cervicovaginal secretions of women with endometriomas compared with healthy surgical controls. Twenty-seven women with unilateral endometrioma and 30 undergoing bilateral tubal ligation were included. AQP9 levels were measured using ELISA, and analyses included correlation, receiver operating characteristic (ROC) curve analysis, and logistic regression adjusted for age, body mass index (BMI), gravida and parity.

Results: Peritoneal fluid AQP9 concentrations were significantly higher in women with endometriomas than in controls (275 [58-669] vs. 171.5 [6.6-507] ng/mL, p = 0.023), whereas serum and cervicovaginal AQP9 levels showed no differences. ROC analysis demonstrated high sensitivity (92.6%) but limited specificity (43.3%). Logistic regression confirmed that peritoneal AQP9 > 128 ng/mL was independently associated with endometrioma (OR 4.40, 95%CI 1.66-29.28, p = 0.025). Serum AQP9 was inversely correlated with endometrioma size (p = 0.008).

Conclusion: Peritoneal AQP9 elevation reflects alterations in the local peritoneal microenvironment, supporting its potential role in the pathophysiology of endometriosis.

Keywords: Endometriosis; aquaporin-9 (AQP9); endometrioma; pathophysiology; peritoneal fluid.

Plain language summary

Peritoneal fluid aquaporin-9 (AQP9) levels were significantly elevated in women with endometriomas compared with healthy controls, independently of age and body mass index. This finding suggests that AQP9 may reflect local inflammatory and signaling changes in the peritoneal environment rather than serving as a systemic biomarker. Understanding AQP9’s role in endometriosis may provide insight into the molecular mechanisms underlying lesion persistence and progression, supporting future research into targeted therapeutic or diagnostic approaches aimed at modulating fluid transport, inflammation, and cellular migration in endometriosis.

MeSH terms

  • Adult
  • Aquaporins* / blood
  • Aquaporins* / metabolism
  • Ascitic Fluid / chemistry
  • Ascitic Fluid / metabolism
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Case-Control Studies
  • Endometriosis* / blood
  • Endometriosis* / diagnosis
  • Endometriosis* / metabolism
  • Endometriosis* / physiopathology
  • Female
  • Humans
  • Prospective Studies
  • ROC Curve

Substances

  • Aquaporins
  • AQP9 protein, human
  • Biomarkers