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

Maneesh N. Singh, Helen F. Stringfellow, Siân E. Taylor, Kate M. Ashton, Mushfika Ahmad, Khalil R. Abdo, Omar Ali El-Agnaf, Pierre L. Martin-Hirsch, Francis L. Martin

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22 Citations (Scopus)

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 γ-SYNUCLEIN (γ-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)α, ERβ and γ-SYN. Immunohistochemical analyses for γ-syn, ERα, 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 γ-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; γ-syn positivity was associated with endothelial cells. An elevation in ERβ was also noted when comparing ectopic to eutopic endometrium; with regard to ERα, this was inconsistent. These results suggest an up-regulation of dioxin-inducible CYP1A1 and γ-SYN occurs in endometriosis. Whether γ-syn may be a novel diagnostic marker for endometriosis remains to be ascertained.

Original languageEnglish
Pages (from-to)655-663
Number of pages9
JournalMolecular Human Reproduction
Volume14
Issue number11
DOIs
Publication statusPublished - 2008
Externally publishedYes

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Keywords

  • γ-synuclein
  • BCL-2
  • CYP1A1
  • Endometriosis
  • Estrogen receptor

ASJC Scopus subject areas

  • Molecular Biology
  • Embryology
  • Cell Biology
  • Genetics
  • Developmental Biology
  • Reproductive Medicine
  • Obstetrics and Gynaecology

Cite this

Singh, M. N., Stringfellow, H. F., Taylor, S. E., Ashton, K. M., Ahmad, M., Abdo, K. R., Ali El-Agnaf, O., Martin-Hirsch, P. L., & Martin, F. L. (2008). Elevated expression of CYP1A1 and γ-SYNUCLEIN in human ectopic (ovarian) endometriosis compared with eutopic endometrium. Molecular Human Reproduction, 14(11), 655-663. https://doi.org/10.1093/molehr/gan056