Aberrant expression of regulators of cell-fate found in eutopic endometrium is found in matched ectopic endometrium among women and in a baboon model of endometriosis

Hapangama DK, D. Hapangama, D K Hapangama, M. Turner, M A Turner, Josephine Drury, J Drury, L. Heathcote, Heathcote L, Yalda Afshar, Y Afshar, Mavrogianis PA, P A Mavrogianis, Patricia A. Mavrogianis, A T Fazleabas, Asgerally T Fazleabas, Fazleabas AT
Human Reproduction · 2010 · vol. 25(11) , pp. 2840–2850 · doi:10.1093/humrep/deq248 · PMID:20858696 · PMC2955559 · W2121367862
Lab / animal OA: bronze CC0 ⤵ 25 in-corpus citations
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Ectopic endometriotic lesions and, later, eutopic endometrium in baboons express proliferative regulators and reduced DNA repair markers, suggesting altered cell fate drives endometriosis.

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Abstract

BACKGROUND: We have recently shown that women with endometriosis express an increased amount of telomerase and nucleolin, with concomitant loss of γ-H2AX in eutopic endometrium. To further examine these selected factors that regulate cell fate, in the pathogenesis of endometriosis, we studied the expression of telomerase, nucleolin, proliferating cell nuclear antigen and γ-H2AX in ectopic endometriotic deposits from women, and in matched eutopic and ectopic endometrial tissue from a baboon model of endometriosis. METHODS: Ectopic active peritoneal endometriotic lesions were collected from seven symptomatic women. Endometriosis was induced in six baboons by intra-peritoneal autologous inoculation of menstrual endometrium. Eutopic and matched ectopic endometrial tissues were collected prior to and 6, 12 and 15 months after the induction of endometriosis as previously described. Eutopic endometrium was also obtained from eight healthy fertile control baboons. Immunohistochemistry was performed as previously described, and telomerase activity was confirmed using the telomeric repeat amplification protocol assay. RESULTS: All active human endometriotic lesions expressed the proliferative markers but showed weak or absent staining for γ-H2AX. A similar expression pattern of these markers was seen in the ectopic lesions of the baboons with induced disease. In these baboons, the eutopic endometrium also showed intense immunoreactivity for all proliferative markers 6-12 months after induction with a parallel loss of γ-H2AX. The opposite staining pattern was seen in eutopic endometrium of healthy animals and in pre-induction endometrium of animals with induced disease. CONCLUSIONS: Endometriotic lesions have excess proliferative potential; in baboons, these were present within 12 months of the initiation of the disease. In eutopic tissue, these changes appear to be induced by the development of endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Choristoma Endometriosis Endometrium Histones Phosphoproteins Proliferating Cell Nuclear Antigen RNA-Binding Proteins Telomerase Animals Animals Choristoma Choristoma Disease Models, Animal Disease Models, Animal Endometriosis Endometriosis Endometrium Endometrium Female Female

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