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Mol. Hum. Reprod. Advance Access originally published online on October 10, 2008
Molecular Human Reproduction 2008 14(11):655-663; doi:10.1093/molehr/gan056
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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

Maneesh N. Singh1,2, Helen F. Stringfellow1, Siân E. Taylor1,2, Kate M. Ashton1, Mushfika Ahmad3, Khalil R. Abdo1, Omar M.A. El-Agnaf3, Pierre L. Martin-Hirsch1,2 and Francis L. Martin2,4

1 Lancashire Teaching Hospitals NHS Trust, Fulwood, Preston, UK 2Lancaster Environment Centre, Lancaster University, Lancaster, UK 3Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates

4 Correspondence address. E-mail: f.martin{at}lancaster.ac.uk

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}, ERβ and {gamma}-SYN. Immunohistochemical analyses for {gamma}-syn, ER{alpha}, ERβ 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 ERβ 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.

Key words: BCL-2/CYP1A1/endometriosis/estrogen receptor/{gamma}-synuclein

Submitted on June 16, 2008; resubmitted on August 31, 2008; accepted on September 30, 2008.


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