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Sustained replication in endometrium of women with endometriosis occurs without evoking a DNA damage response

Lookup NU author(s): Mandy Maddick, Dr Carmen Martin-Ruiz, Professor Thomas von Zglinicki

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Abstract

BACKGROUND: To test our hypothesis that eutopic secretory phase endometrium from women with endometriosis is similar to proliferative phase endometrium from fertile women without endometriosis, we explored the expression of regulators of cell fate across the menstrual cycle. METHODS: Endometrial biopsies were taken from 73 women, comprising 38 women with surgically diagnosed active peritoneal endometriosis (Group 1) and 35 fertile women without endometriosis (Group 2). Nucleolin, proliferating cell nuclear antigen (PCNA), telomerase and histone γ-H2AX expression was evaluated by immunohistochemistry and mean telomere length (TL) by quantitative PCR. RESULTS: We have immunolocalized nucleolin and γ-H2AX in the benign premenopausal endometrium for the first time. All markers were present in the proliferative phase endometrium of all women. In Group 2, during the secretory phase, proliferative markers declined with a paradoxical increase in stromal γ-H2AX. Women in Group 1, however, showed a persistent immunoreactivity for the proliferative markers, while the staining for γ-H2AX decreased in secretory endometrium (P < 0.05). This difference between groups was significant in both stroma and glands for nucleolin (P < 0.0001), PCNA (P < 0.01) and γ-H2AX (P < 0.05) in the secretory phase. We showed a positive correlation between mean TL and nucleolin expression (glandular r = 0.37, P = 0.002; stromal r = 0.4, P = 0.001), telomerase immunoreactivity (glandular r = 0.33, P = 0.009; stromal r = 0.4, P = 0.001) and glandular PCNA (r = 0.35, P = 0.004), whereas a negative correlation was seen between mean TL and γ-H2AX (r = -0.28, P = 0.04). CONCLUSIONS: These findings demonstrate that the state of replication seen in secretory phase endometrium from women with active peritoneal endometriosis is not a simple extension of the proliferative phase. © The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.


Publication metadata

Author(s): Hapangama DK, Turner MA, Drury JA, Quenby S, Hart A, Maddick M, Martin-Ruiz C, von Zglinicki T

Publication type: Article

Publication status: Published

Journal: Human Reproduction

Year: 2009

Volume: 24

Issue: 3

Pages: 687-696

ISSN (print): 0268-1161

ISSN (electronic): 1460-2350

Publisher: Oxford University Press

URL: http://dx.doi.org/10.1093/humrep/den416

DOI: 10.1093/humrep/den416


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