Abstract
Telomeres protect chromosomal ends and they are maintained by the specialised enzyme, telomerase. Endometriosis is a common gynaecological disease and high telomerase activity and higher hTERT levels associated with longer endometrial telomere lengths are characteristics of eutopic secretory endometrial aberrations of women with endometriosis. Our ex-vivo study examined the levels of hTERC and DKC1 RNA and dyskerin protein levels in the endometrium from healthy women and those with endometriosis (n = 117). The in silico study examined endometriosis-specific telomere- and telomerase-associated gene (TTAG) transcriptional aberrations of secretory phase eutopic endometrium utilising publicly available microarray datasets. Eutopic secretory endometrial hTERC levels were significantly increased in women with endometriosis compared to healthy endometrium, yet dyskerin mRNA and protein levels were unperturbed. Our in silico study identified 10 TTAGs (CDKN2A, PML, ZNHIT2, UBE3A, MCCC2, HSPC159, FGFR2, PIK3C2A, RALGAPA1, and HNRNPA2B1) to be altered in mid-secretory endometrium of women with endometriosis. High levels of hTERC and the identified other TTAGs might be part of the established alteration in the eutopic endometrial telomerase biology in women with endometriosis in the secretory phase of the endometrium and our data informs future research to unravel the fundamental involvement of telomerase in the pathogenesis of endometriosis.
Highlights
Telomeres are specialised nucleoprotein complexes at the chromosomal ends containing repeated nucleotide sequences ((TTAGGG)n) and shelterin proteins [1]
High Telomerase activity (TA) levels, higher hTERT gene expression and hTERT protein levels associated with longer mean endometrial telomere length (TL) have all been reported to be characteristics of such abnormalities specific to eutopic secretory endometrium of women with endometriosis when compared with the endometrium of healthy women [7,14,18,19,20,21]
Using a comprehensive telomere- and telomerase-associated genes (TTAGs) list that was compiled in our previous work [22], differentially regulated telomereand telomerase-associated gene (TTAG) were examined in published human endometrial microarray datasets from women with and without endometriosis, which were selected according to a strict predetermined criteria
Summary
Telomeres are specialised nucleoprotein complexes at the chromosomal ends containing repeated nucleotide sequences ((TTAGGG)n) and shelterin proteins [1]. This phenomenon of retrograde menstruation occurs in almost all women [13] while the prevalence of endometriosis in the general population is only 10–15% of women This theory had subsequently been modified to propose that eutopic endometrium shed by women with endometriosis to have particular aberrations, enhancing its ectopic growth [14,15]. High TA levels, higher hTERT gene expression and hTERT protein levels associated with longer mean endometrial telomere length (TL) have all been reported to be characteristics of such abnormalities specific to eutopic secretory endometrium of women with endometriosis when compared with the endometrium of healthy women [7,14,18,19,20,21]. Using a comprehensive telomere- and telomerase-associated genes (TTAGs) list that was compiled in our previous work [22], differentially regulated TTAGs were examined in published human endometrial microarray datasets from women with and without endometriosis, which were selected according to a strict predetermined criteria
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