Peripheral Blood Telomere Content Is Greater in Patients With Endometriosis Than in Controls

Dracxler, Roberta; Oh, Cheongeun; Kalmbach, Keri; Wang, F.; Liu, L.; Kallas, Esper G.; Giret, María Teresa Maidana; Seth-Smith, M.L.; Antunes, Danielle Mota Fontes; Keefe, David L.; Abrão, Maurício Simões

doi:10.1177/1933719114527353

Cited by 22 publications

(18 citation statements)

References 29 publications

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“…However, the seemingly vigorous endometrial regulation of telomerase via ovarian hormones and the fact that TA levels are high and constitutively expressed in proliferating endometrial epithelial cells may be responsible for the apparently rare incidence of such transformation ( Zafrakas et al ., 2014 ; Ness et al ., 2015 ). TL in peripheral lymphocytes of women with endometriosis compared to healthy controls did not differ in our studies ( Hapangama et al ., 2008 ; Hapangama et al ., 2009 ) while others have reported longer telomeres in PBMCs from women with endometriosis ( Dracxler et al ., 2014 ). The reason for this observed difference could be attributed to the influence of different demographic features known to affect PMBC TL such as age, BMI and ethnicity.…”

Section: The Endometriummentioning

confidence: 92%

Implications of telomeres and telomerase in endometrial pathology

Hapangama

Kamal

Saretzki

2016

Hum. Reprod. Update

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BACKGROUNDEukaryotic chromosomal ends are linear and are protected by nucleoprotein complexes known as telomeres. The complex structural anatomy and the diverse functions of telomeres as well as the unique reverse transcriptase enzyme, telomerase that maintains telomeres are under intensive scientific scrutiny. Both are involved in many human diseases including cancer, but also in ageing and chronic disease such as diabetes. Their intricate involvement in many cellular processes and pathways is being dynamically deciphered in many organs including the endometrium. This review summarizes our current knowledge on the topic of telomeres and telomerase and their potential role in providing plausible explanations for endometrial aberrations related to common gynaecological pathologies.OBJECTIVE AND RATIONALEThis review outlines the recent major findings in telomere and telomerase functions in the context of endometrial biology. It highlights the contemporary discoveries in hormonal regulation, normal endometrial regeneration, stem cells and common gynaecological diseases such as endometriosis, infertility, recurrent reproductive failure and endometrial cancer (EC).SEARCH METHODSThe authors carried out systematic PubMed (Medline) and Ovid searches using the key words: telomerase, telomeres, telomere length, human telomerase reverse transcriptase, telomeric RNA component, with endometrium, hormonal regulation, endometrial stem/progenitor cells, endometrial regeneration, endometriosis, recurrent miscarriage, infertility, endometrial hyperplasia, EC and uterine cancer. Publications used in this review date from 1995 until 31st June 2016.OUTCOMESThe human endometrium is a unique somatic organ, which displays dynamic telomerase activity (TA) related to the menstrual cycle. Telomerase is implicated in almost all endometrial pathologies and appears to be crucial to endometrial stem cells. In particular, it is vital for normal endometrial regeneration, providing a distinct route to formulate possible curative, non-hormonal therapies to treat chronic endometrial conditions. Furthermore, our current understanding of telomere maintenance in EC is incomplete. Data derived from other malignancies on the role of telomerase in carcinogenesis cannot be extrapolated to EC because unlike in other cancers, TA is already present in proliferating healthy endometrial cells.WIDER IMPLICATIONSSince telomerase is pivotal to endometrial regeneration, further studies elucidating the role of telomeres, telomerase, their associated proteins and their regulation in normal endometrial regeneration as well as their role in endometrial pathologies are essential. This approach may allow future development of novel treatment strategies that are not only non-hormonal but also potentially curative.

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Section: The Endometriummentioning

confidence: 92%

Implications of telomeres and telomerase in endometrial pathology

Hapangama

Kamal

Saretzki

2016

Hum. Reprod. Update

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“…Consistent with the potential role of TP53 in fibrogenesis in endometriosis, endometriotic cells are reported to have longer telomeres and higher telomerase expression. [111][112][113] In addition, miR-125b is found to be critical for FMT and fibrosis, and to promote fibroblast proliferation through suppression of TP53. 114 Remarkably, miR-125b upregulation has been reported in endometriosis.…”

Section: Tp53mentioning

confidence: 99%

Cancer driver mutations in endometriosis: Variations on the major theme of fibrogenesis

Guo

2018

Reprod Medicine & Biology

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BackgroundOne recent study reports cancer driver mutations in deep endometriosis, but its biological/clinical significance remains unclear. Since the natural history of endometriosis is essentially gradual progression toward fibrosis, it is thus hypothesized that the six driver genes reported to be mutated in endometriosis (the RP set) may play important roles in fibrogenesis but not necessarily malignant transformation.MethodsExtensive PubMed search to see whether RP and another set of driver genes not yet reported (NR) to be mutated in endometriosis have any roles in fibrogenesis. All studies reporting on the role of fibrogenesis of the genes in both RP and NR sets were retrieved and evaluated in this review.ResultsAll six RP genes were involved in various aspects of fibrogenesis as compared with only three NR genes. These nine genes can be anchored in networks linking with their upstream and downstream genes that are known to be aberrantly expressed in endometriosis, piecing together seemingly unrelated findings.ConclusionsGiven that somatic driver mutations can and do occur frequently in physiologically normal tissues, it is argued that these mutations in endometriosis are not necessarily synonymous with malignancy or premalignancy, but the result of enormous pressure for fibrogenesis.

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“…Analysis of menstrual tissue samples from affected women showed that endometriosis patients have significantly more fragments of the basalis layer in the flow than healthy controls [70]. Cells from menstrual blood of patients also have longer than average telomeres, which is in agreement with an enhanced stem cell presence [71]. According to this model, long-lived stem cells from the basalis are disseminated and give rise to endometriotic lesions.…”

Section: Uterine Endometrial Stem Cellsmentioning

confidence: 61%