Endometriosis is Associated With Aberrant Endometrial Expression of Telomerase and Increased Telomere Length

Endometriosis is Associated With Aberrant Endometrial Expression of Telomerase and Increased Telomere Length - D K. Hapangama - M A. Turner - J A. Drury - S Quenby - G Saretzki - C Martin-Ruiz - T Von Zglinicki By protecting eukaryotic linear chromosomal ends, telomeres are critical in maintaining chromosomal integrity and cellular stability. The expression of telomerase correlates specifically with cellular proliferation, and most endometrial cancers express high levels. This prospective pilot study tested the hypothesis that endometriosis is associated with abnormal expression of telomerase and telomere lengthening in the endometrium. Endometrial expression of the human telomerase enzyme and telomere length (TL) were compared in 29 women with symptomatic, surgically diagnosed endometriosis – about half of whom had severe disease – and 27 healthy, fertile women in whom laparoscopy ruled out endometriosis. Seventeen and 15 women, respectively, had endometrial biopsy on or about cycle day 21, and 12 women in each group were biopsied on or about day 26. Expression of telomerase and estrogen receptor β (ERβ) was estimated immunohistochemically and mean TL by the quantitative polymerase chain reaction technique. In healthy fertile women, the endometrium exhibited absent or, at most, weak telomerase immunoreactivity throughout the luteal phase. Telomerase activity increased significantly during the implantation window and also in the premenstrual phase in women with endometriosis. At the same time, stromal and vascular immunostaining for ERβ was lost. The mean endometrial TL was significantly greater in women with endometriosis during the implantation window. Peripheral blood TL values correlated positively with circulating levels of estradiol. Circulating progesterone levels were similar in women with and those without endometriosis. The investigators interpret these findings to signify abnormal endometrial expression of telomerase and consequent cellular changes that promote endometrial-cell proliferation, thereby contributing to the development of endometriosis.