Peptidomic Analysis of Endometrial Tissue from Patients with Ovarian Endometriosis

Ovarian endometriosis (OvE) is ovarian cyst that is lined with endometrial tissue. They are found in 17-44% of women with endometriosis. Their clinical manifestations include pelvic pain, dysmenorrhea, dyspareunia, and infertility. Although the incidence of OvE has increased yearly, the exact pathogenesis of OvE is still unclear. We used peptidomics, an emerging branch of proteomics, to identify differentially expressed peptides in order to determine the possible roles of these peptides in the pathogenesis of OvE.

The ectopic and eutopic endometria of OvE were used to extract peptides with 10-kDa molecular weight cutoff filters, and the peptide precursor proteins were then identified with PEAKS software, followed by quantification with the TMT labeling method and subsequent analysis by liquid chromatography-tandem mass spectrometry. Gene ontology (GO) analysis, pathway analysis, SMART, and SABLE were used to study the possible functions of these peptide according to their precursor proteins' function. The effects of peptides derived from VCAM-1 (PDFV) on endometrial stromal cell (ESC) migration and invasion were examined with wound healing assays and Transwell assays and the expression of E-cadherin was detected by western blotting.

A total of 491 peptides were identified with abundant differences between the two groups of samples (p < 0.05, and absolute fold change ≥ 2). SMART and SABLE database showed that 42 of the 491 peptides were located in the conserved structural domains of their protein precursors and contained secondary structure and, among them, 2 peptides' precursor proteins were associated with the cell proliferation. Additionally, 5 peptides' precursor proteins were associated with endometriosis. Our study confirmed that PDFV promoted ESC migration and invasion and reduced E-cadherin expression (p < 0.05).

PDFV and its precursor protein VCAM-1 may be involved in the process of OvE formation by reducing the expression of E-cadherin. The peptidomics analysis provides new insight for future studies of the mechanisms of OvE development.