Hum. Reprod. Advance Access originally published online on May 2, 2008
Human Reproduction 2008 23(7):1511-1519; doi:10.1093/humrep/den172
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Endometriosis is associated with aberrant endometrial expression of telomerase and increased telomere length
1 School of Reproductive and Developmental Medicine, University of Liverpool, Liverpool Women's Hospital, Crown Street, Liverpool L8 7SS, UK 2 Crucible Laboratory, Life Knowledge Park, University of Newcastle, Newcastle upon Tyne NE4 6BE, UK 3 Henry Wellcome Laboratory for Biogerontology Research, University of Newcastle, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE, UK
4 Correspondence address. E-mail: dharani.hapangama{at}liverpool.ac.uk
BACKGROUND: In order to test our hypothesis that endometriosis is associated with abnormal expression of telomerase and telomere lengthening in endometrium, we assessed endometrial expression of the human telomerase enzyme and telomere length (TL).
METHODS: This prospective pilot study, included 29 women with symptomatic, surgically diagnosed endometriosis (Group 1) and 27 healthy, fertile, symptom-free women without endometriosis (Group 2, confirmed by laparoscopy). Seventeen women in Group 1 and 15 women in Group 2 had endometrial biopsies taken on Day 21 ± 2 of the cycle. A further 12 women in each group were biopsied on Day 26 ± 2. Telomerase and estrogen receptor beta (ERβ) expression was evaluated by immunohistochemistry. Mean TL was determined by quantitative PCR.
RESULTS: The endometria of fertile healthy women showed either weak or no telomerase immunoreactivity throughout the luteal phase. Immunostaining for telomerase was significantly increased during the implantation window and the premenstrual endometria of women with endometriosis (P < 0.0001). This was associated with a loss of stromal and vascular ERβ immunostaining (P < 0.05). The mean TL were significantly longer in endometria of women with endometriosis during the implantation window (P = 0.005), indicating the biological relevance of our novel finding of telomerase in benign endometrium. There was positive correlation of the circulating estradiol with peripheral blood TL in women.
CONCLUSIONS: We speculate that aberrant endometrial expression of telomerase mediates alterations in cell fate that enhance proliferation, contributing to the pathogenesis of endometriosis.
Key words: telomerase/endometriosis/telomere length/telomerase repeat amplification protocol/secretory phase endometrium
Submitted on July 16, 2007; resubmitted on February 10, 2008; accepted on April 8, 2008.