A Pilot Proteomic Study of Vestibular Fluid From Patients With Vulvodynia

Abstract

Objective: Many women are affected by vulvodynia, but medical therapies to date have proven ineffective. We performed a pilot study using gel-based proteomics to develop a map of proteins present in vaginal/vestibular secretions and identify proteins that could be considered for future evaluation as potential therapeutic targets. Materials and Methods:We collected vestibular fluid from 4 controls and 4 patients with vulvodynia by placing a cotton swab in the vestibule and extracting the absorbed proteins. The proteins underwent 2-dimensional difference gel electrophoresis and mass spectrometry to develop a protein map. Immunohistochemistry was used to validate proteomic findings.Results: A map was constructed of 32 of the more abundant proteins in vestibular fluid and their levels compared in control subjects and vulvodynia patients. Among these were annexin A1, interleukin 1 receptor antagonist, protein S100 A9, and a number of antiproteases and proteases. Many of these proteins differed by at least 50% between groups, but only annexin A1, one of the protease inhibitors, and immunoglobulin G κ chain were significantly different. The results with annexin A1 were validated by similar findings with immunohistochemistry. Conclusions:The findings of this pilot study demonstrate a set of vestibule mucosa proteins that differ significantly-either increasing or decreasing-in vulvodynia patients compared with controls, and several others that exhibited greater than 1.5-fold change but did not reach statistical significance. This study constitutes a proof-of-principle that an open, unbiased proteomic approach can identify molecular participants in vulvodynia, some of which had not been identified to date by hypothesis-driven studies.

Is Vulvodynia Associated With an Altered Vaginal Microbiota?: A Systematic Review

“…Furthermore, investigating the changes in the vaginal microbiota of vulvodynia patients over time can be a worthwhile area of future research, as it can provide valuable insights into the temporality of vulvodynia. Using functional, rather than taxonomic, approaches could also provide valuable insights, as a pilot proteomics study recently revealed that certain protein levels were significantly different in the vestibular fluid of vulvodynia patients 49 . Lastly, investigating the potential link between vulvodynia and the gut and urinary microbiota could be an interesting area for future research beyond the vaginal microbiota.…”

“…Using functional, rather than taxonomic, approaches could also provide valuable insights, as a pilot proteomics study recently revealed that certain protein levels were significantly different in the vestibular fluid of vulvodynia patients. 49 Lastly, investigating the potential link between vulvodynia and the gut and urinary microbiota could be an interesting area for future research beyond the vaginal microbiota.…”

Chronic Pelvic Pain, Vulvar Pain Disorders, and Proteomics Profiles: New Discoveries, New Hopes

“…Annexin upregulation has been found in women with vulvodynia (annexin 1) and in adenomyosis samples; interestingly, these proteins are involved in the induction of both metastatic potential and proangiogenic capacity in endometrial cells. Annexin 1 is phospholipid-binding protein active in membrane trafficking and has been related to mast cell granules, one of the most important mechanisms implicated in the genesis of vulvodynia [35]. Annexin 2 is a pleiotropic protein with a mechanism of action fully related to the site of its activity.…”

“…MacNeill et al evaluated protein abundance in eight women with vulvodynia to obtain new potential therapeutic targets [35]. Secretions at vaginal/vestibular sites were collected for protein mapping using gel proteomics, two-dimensional difference gel elec-trophoresis, and mass spectrometry.…”