Increased Telomerase Activity and Human Telomerase Reverse Transcriptase mRNA Expression in the Endometrium of Patients with Endometriosis

Abstract

Endometriosis-the implantation of endometrial tissue outside its normal uterine location-may occur in as many as 15% of women of reproductive age, but its pathogenesis still is not fully understood. Conceivably the affected endometrium has endogenous abnormalities that predispose to the disease. While not a premalignant disease, endometriosis does undergo malignant transformation. The investigators studied the potential for limitless replication in endometrial biopsy specimens from 30 women with endometriosis and 30 normal women. The expression of human telomerase reverse transcriptase (hTERT) mRNA was quantified by the real-time reverse transcriptase-polymerase chain reaction assay, and telomerase activity by the telomerase repeat amplification protocol assay. Expression of hTERT mRNA was identified in 90% of specimens from women with endometriosis and in 80% of control samples, but women in the disease group had significantly higher levels. Expression was maximal in the late proliferative phase and minimal in the late secretory phase. Levels of expression were highest in the proliferative phase of the cycle in women with endometriosis and lowest in the secretory phase in control women. Endometrial telomerase activity was identified in 90% of women in both groups. Those with moderate-to-severe endometriosis had significantly higher activity levels than did control women. When analyzed by menstrual phase, telomerase activity followed a pattern similar to that of hTERT mRNA expression. Levels of both hTERT mRNA and telomerase activity increased with the severity of disease. No significant correlation was found between telomerase activity and the size of the endometriotic cyst. Levels of hTERT mRNA and telomerase activity correlated significantly, positively, and linearly with one another. These findings suggest that the replication potential of endometrial tissue in the peritoneal cavity is a critical factor in the development of viable endometriotic implants, and therefore may have an important role in the pathogenesis of endometriosis.