The human tubal lavage proteome reveals biological processes that may govern the pathology of hydrosalpinx

Our plain-English summary of The human tubal lavage proteome reveals biological processes that may govern the pathology of hydrosalpinx, by E. Yohannes, A.A. Kazanjian, M.E. Lindsay, et al (Scientific Reports, 2019).

The study

• Authors: E. Yohannes, A.A. Kazanjian, M.E. Lindsay, D.T. Fujii, N. Ieronimakis, G.E. Chow, R.D. Beesley, R.J. Heitmann, R.O. Burney
• Journal: Scientific Reports
• Published: 2019;9(1):8980
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Hydrosalpinx, the blockage of fallopian tubes, can result from pelvic inflammatory disease. Hydrosalpinx is a cause of infertility and negatively impacts in vitro fertilization. To better understand the pathobiology of hydrosalpinx, we compared the proteome of lavages from disease vs. healthy fallopian tubes. Results indicate a disruption of redox homeostasis and activation of the complement system, immune cell infiltration, and phagocytosis; pathways that may drive tubal injury. To our surprise among the most prominent proteins with hydrosalpinx was mesothelin (MSLN), which until now has only been associated with epithelial malignancies. Analogous to mesothelioma and ovarian carcinoma, a significant increase of MSLN was detected in plasma from patients with hydrosalpinx. This finding suggests MSLN may provide clinical diagnosis in lieu of the current approaches that require invasive imaging. Importantly, these findings implicate MSLN in a benign disease, indicating that the activation and role of MSLN is not restricted to cancer.

In plain English

This laboratory study compared fluid from blocked, fluid-filled fallopian tubes (hydrosalpinx) with rinse fluid from healthy tubes in volunteer women aged 18 to 45 at Madigan Army Medical Center in Tacoma, Washington. It did not study asbestos or any fiber exposure. Using mass spectrometry, the authors identified 519 proteins. Of these, 76 were more abundant and 40 less abundant in hydrosalpinx fluid. A quarter of the more abundant proteins were linked to the complement system, part of the body's immune defenses. Enzymes that protect against oxidative damage were lower. The protein mesothelin was among the most overabundant, with no overlap between 10 hydrosalpinx and 16 healthy samples. In blood plasma, mean mesothelin was 21.52 ng/mL in 9 women with hydrosalpinx versus 13.60 ng/mL in 9 healthy controls (p less than 0.05). The authors concluded that finding mesothelin in hydrosalpinx was novel and may have diagnostic value. They noted possible blood contamination, that not all women with high tube-fluid mesothelin had high plasma levels, and that a larger group of patients is needed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory comparison (proteomics study) of fallopian tube fluid from women with hydrosalpinx versus healthy controls. Selected proteins were checked by immunoblotting and tissue staining, and plasma mesothelin was measured by ELISA.
• Who was studied: Volunteer women aged 18 to 45 at Madigan Army Medical Center (Tacoma, Washington). Healthy controls were fertile women having tubal reversal surgery, and the hydrosalpinx group was confirmed by imaging and at laparoscopy. Group sizes were 16 control and 10 hydrosalpinx lavages for protein counting, 5 control and 6 hydrosalpinx samples for immunoblotting, and 9 per group for plasma. No study dates are given.
• Exposure: No asbestos or fiber exposure was studied. The comparison was between diseased (hydrosalpinx) and healthy fallopian tubes.
• Main results:
  • Of 519 proteins identified, 116 differed between groups: 76 were up-regulated and 40 down-regulated in hydrosalpinx fluid.
  • 25% of the proteins up-regulated in hydrosalpinx were linked to the complement pathway.
  • Proteins related to reactive oxygen species generation were increased in hydrosalpinx (Z-score 2.44), and proteins that break down hydrogen peroxide were decreased (Z-score -2.16).
  • By immunoblot, hydrosalpinx fluid contained about 11-fold less TXN and 4-fold less TXNRD1 than healthy lavages.
  • Mesothelin levels in tube fluid did not overlap between hydrosalpinx (n = 10) and control (n = 16) samples.
  • Mean plasma mesothelin was 21.52 plus or minus 2.81 ng/mL in women with hydrosalpinx versus 13.60 plus or minus 0.89 ng/mL in healthy controls (p less than 0.05), with 9 women per group.
  • Of the nine women with hydrosalpinx who had elevated mesothelin in tube fluid, six had higher plasma mesothelin.
• The authors' conclusion: The authors concluded that identifying mesothelin in hydrosalpinx is a novel finding that may provide diagnostic value. They also concluded that their results implicate the complement pathway and oxidative stress as potential mechanisms of tubal damage and embryotoxicity.
• Limitations the authors state:
  • Proteomics results may have been confounded by blood contamination, particularly in lavage specimens.
  • The method may not have reliably detected low-abundance proteins.
  • Not all women with higher mesothelin in tube fluid had higher plasma levels.
  • Plasma mesothelin would not be able to distinguish hydrosalpinx in women at risk for ovarian cancer.
  • A larger cohort is needed to determine the diagnostic accuracy of mesothelin for hydrosalpinx.
  • The statistical method (DESeq2) was originally developed for RNA data and needs further validation for proteomics.

Topics

Medical terms in this study, explained in our Lexicon: Pathology, Phagocytosis, Mesothelin, Mesothelioma, Carcinoma.

Related studies

• Proteome analysis of bronchoalveolar lavage in individuals from Metsovo, nonoccupationally exposed to asbestos — D.T. Archimandriti, Y.A. Dalavanga, et al. (2009)
• Nongynecologic metastases to fallopian tube mucosa: a potential mimic of tubal high-grade serous carcinoma and benign tubal mucinous metaplasia or nonmucinous hyperplasia — J.T. Rabban, P. Vohra, et al. (2015)
• Proteome screening of pleural effusions identifies galectin 1 as a diagnostic biomarker and highlights several prognostic biomarkers for malignant mesothelioma — F. Mundt, H.J. Johansson, et al. (2014)
• Proteomes of Residual Tumors in Curcumin-Treated Rats Reveal Changes in Microenvironment/Malignant Cell Crosstalk in a Highly Invasive Model of Mesothelioma — D.L. Pouliquen, M. Malloci, et al. (2022)
• Lymphoid Organ Proteomes Identify Therapeutic Efficacy Biomarkers Following the Intracavitary Administration of Curcumin in a Highly Invasive Rat Model of Peritoneal Mesothelioma — D.L. Pouliquen, A. Boissard, et al. (2021)
• Comparative proteomics and pulmonary toxicity of instilled single-walled carbon nanotubes, crocidolite asbestos, and ultrafine carbon black in mice — J.G. Teeguarden, B.J. Webb-Robertson, et al. (2011)

Browse more research in Scientific Reports, or return to medical research.