Telomerase in the ovary

Abstract

Telomerase, an enzyme complex that binds the chromosome ends (telomeres) and maintains telomere length and integrity, is present in germ cells, proliferative granulosa cells, germline stem cells, and neoplastic cells in the ovary, but it is absent in differentiated or aged cells. Activation of telomerase in the ovary underpins both benign and malignant cell proliferation in several compartments, including the germ cells, membrana granulosa, and the ovarian surface epithelium. The difference in telomerase operation between normal and abnormal cell proliferations may lie in the mechanisms of telomerase activation in a deregulated manner. Recent studies have implicated telomerase activity in ovarian cancer as well as oogenesis and fertility. Inhibition of telomerase and the shortening of telomeres are seen in occult ovarian insufficiency. Studies of how telomerase operates and regulates ovary development may provide insight into the development of both germ cells for ovarian reproductive function and neoplastic cells in ovarian cancer. The current review summarizes the roles of telomerase in the development of oocytes and proliferation of granulosa cells during folliculogenesis and in the process of tumorigenesis. It also describes the regulation of telomerase by estrogen in the ovary.

A splicing variant of TERT identified by GWAS interacts with menopausal estrogen therapy in risk of ovarian cancer

“…Presently, it is unclear whether telomerase activation helps in the uncontrolled cellular proliferation of existing cancer cells or in the preservation of a non-malignant phenotype by maintaining the replicative longevity of ovarian cells. 35 Our results appear to support the latter.…”

Delay in oocyte aging in mice by the antioxidant N-acetyl-l-cysteine (NAC)

“…Thus, protection against oxidative stress by NAC could directly contribute to maintenance of telomeres in aging mouse ovaries. Telomerase activity and maintenance of telomere length are critical for high survival and proliferation of germ cells and granulosa cells, and reduced telomerase activity plays an integral role in granulosa cell apoptosis and follicular atresia (Lavranos et al, 1999;Yamagata et al, 2002;Liu and Li, 2010). Telomerase activity declines in the human ovary with age (Kinugawa et al, 2000).…”

Telomere Length and Genetic Variation in Telomere Maintenance Genes in Relation to Ovarian Cancer Risk

“…Telomerase activity has been identified in some normal ovarian and fallopian tube tissue and is thought to contribute in a controlled manner to oogenesis and fertility (6, 7). Conversely, telomerase is not detectable in premalignant lesions but is upregulated in 90-97% of ovarian cancers, suggesting deregulation of telomerase is a step in ovarian carcinogenesis (6).…”

“…Conversely, telomerase is not detectable in premalignant lesions but is upregulated in 90-97% of ovarian cancers, suggesting deregulation of telomerase is a step in ovarian carcinogenesis (6). Twin studies suggest that the majority (40-80% heritability) of interindividual variation in telomere length is genetic (8, 9).…”