Receptive window might be shorter in patients with endometriosis and lesions cyclically prepare for implantation

Abstract

ObjectiveTo investigate whether endometrial receptivity is affected in patients with endometriosis using podocalyxin (PCX) as a functional biomarker; to study how endometriotic lesions display PCX and the potential pathological implications. DesignWe have previously reported that PCX, an anti-adhesion glycoprotein and barrier protector, is dynamically regulated in the endometrium and acts as a key negative regulator of epithelial receptivity. Early in the cycle both luminal epithelium (LE, lining the endometrial surface) and glandular epithelium (GE, residing within the tissue) strongly express PCX, but in the receptive window PCX is selectively down-regulated in LE, switching the endometrial surface to an adhesive state for embryo attachment/implantation; meanwhile PCX expression is maintained in GE until post-receptivity. Here, we immuno-stained PCX in endometrial tissues and ectopic lesions biopsied across the menstrual cycle from patients with endometriosis (EOS, n=41), and compared to endometrium of non-endometriosis controls (Non-EOS, n=55). We further investigated how PCX changes observed in ectopic lesions may influence their adhesive capacity. SubjectsWomen without and with endometriosis. ExposureN/A. Main Outcome MeasuresThe window of endometrial receptivity might be shorter in patients with endometriosis; ectopic sites also down-regulate PCX cyclically, mirroring the eutopic endometrial cells in preparing for receptivity to increase their adhesion potential. ResultsEndometrial PCX levels were comparable between non-EOS and EOS early in the cycle, and in both groups PCX is down-regulated in LE during the expected window of receptivity, however, in EOS endometrium PCX is reduced earlier in GE as if the receptive window were shorter. In endometriotic lesions, PCX was detected in endometrial LE- and GE-like cells plus mesothelial cells enveloping peritoneal organs, but PCX was cyclically lost specifically in LE-like cells and reduced in GE-like cells as seen in the eutopic endometrium, which however may increase their adhesion potential to nearby organs (overlaid by mesothelial cells). This speculation was further corroborated in an in vitro model showing endometrial epithelial cells with lower PCX were indeed more adhesive to mesothelial cells. ConclusionEndometrial receptivity is subtly affected in patients with endometriosis with a shorter window. Cyclic down-regulation of PCX in ectopic sites may have pathological consequences.