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

D K Hapangama, Dharani K. Hapangama, M A Turner, M. Turner, J A Drury, Josephine Drury, Siobhan Quenby, S Quenby, A Hart, Mandy Maddick, M Maddick, C Martin-Ruiz, Carmen Martín-Ruiz, Thomas von Zglinicki, T von Zglinicki
Human Reproduction · 2008 · vol. 24(3) , pp. 687–696 · doi:10.1093/humrep/den416 · PMID:19088109 · W2150908847
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Endometrium from women with endometriosis showed sustained proliferation markers and decreased DNA damage response in the secretory phase compared to controls.

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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 gamma-H2AX expression was evaluated by immunohistochemistry and mean telomere length (TL) by quantitative PCR. RESULTS: We have immunolocalized nucleolin and gamma-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 gamma-H2AX. Women in Group 1, however, showed a persistent immunoreactivity for the proliferative markers, while the staining for gamma-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 gamma-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 gamma-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.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

DNA Damage DNA Replication Endometriosis Endometrium Adolescent Adult Biopsy Endometriosis Endometriosis Endometrium Endometrium Female Histones Histones Humans Immunohistochemistry Immunohistochemistry Infertility Infertility Middle Aged

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