Elevated expression of CYP1A1 and gamma-SYNUCLEIN in human ectopic (ovarian) endometriosis compared with eutopic endometrium

Abstract

Endometriosis is a debilitating disease in which apoptotic, genetic, immunological, angiogenic and environmental factors have been implicated. Endocrine-disrupting agents (e.g. dioxins) might be involved. Dioxins, via the arylhydrocarbon receptor (AhR), induce estrogen-metabolizing enzymes CYP1A1 and CYP1B1. Elevated expression of gamma-SYNUCLEIN (gamma-SYN) has been associated with hormone-related conditions. Tissue sets consisting of eutopic and ectopic (ovarian) endometrium from patients with stage 3 or 4 endometriosis were obtained. Following RNA extraction and reverse transcription, quantitative real-time reverse transcriptase-polymerase chain reaction was performed for anti-apoptotic B-cell leukaemia/lymphoma 2 (BCL-2), CYP1A1, CYP1B1, estrogen receptor (ER)alpha, ER beta and gamma-SYN. Immunohistochemical analyses for gamma-syn, ER alpha, ER beta and CYP1A1 were also conducted. A 3-9-fold increase in intra-individual expression of CYP1A1 in ectopic (ovarian) endometrium compared with eutopic tissue was observed; immunohistochemical analyses pointed to CYP1A1 being localized to the glandular epithelium. This intra-individual expression profile was not observed for CYP1B1 or BCL-2. However, a 5-53-fold intra-individual increase in gamma-SYN expression was also demonstrated in six of nine tissue sets (a further two showed an increase that was not considered significant) when comparing ectopic to eutopic endometrium; gamma-syn positivity was associated with endothelial cells. An elevation in ER beta was also noted when comparing ectopic to eutopic endometrium; with regard to ER alpha, this was inconsistent. These results suggest an up-regulation of dioxin-inducible CYP1A1 and gamma-SYN occurs in endometriosis. Whether gamma-syn may be a novel diagnostic marker for endometriosis remains to be ascertained.