Alternation of ten-eleven translocation 1, 2, and 3 expression in eutopic endometrium of women with endometriosis-associated infertility

Abstract

Little is known about the differences in ten-eleven translocation 1, 2, and 3 (TET1-3) expression in the endometrial phases in eutopic endometrium from infertile women with endometriosis (IWE) and fertile women without endometriosis (FW). Using RT-qPCR and western blot analysis, we assessed the TET expression in the mid-follicular and mid-luteal phases in eutopic endometrium from IWE (n = 38) and FW (n = 18). Both IWE and FW underwent laparoscopic and histological examinations for endometriosis. In the mid-luteal eutopic endometrium in IWE, compared to that of FW, we found significantly reduced levels of TET1 transcripts and proteins (p = .001 and p = .003, respectively) at the severity stage of I/II (p = .029 and p = .003, respectively) and transcripts only at the severity stage of III/IV (p = .003). In the mid-follicular eutopic endometrium of IWE, compared to that of FW, there was a statistically significant reduction in TET2 transcript levels at the severity stage of III/IV (p = .037). Compared to the mid-follicular endometrium, we found a statistically significant increase in TET3 transcript levels during the mid-luteal phase in the eutopic endometrium of all IWE (p = .034) and in the severity stage of III/IV (p = .025). We observed a change in the expression levels of TET1-3 in the eutopic endometrium of IWE.

Could DNA hydroxymethylation be crucial in influencing steroid hormone signaling in endometrial biology and endometriosis?

“…There has been conflicting data on the expression and regulation of DNMTs in the endometrium, which implies the need for additional studies. As mentioned previously, studies by Ciesielski et al (), Roca et al (), and Szczepanska et al (), suggest the involvement of TETs in the onset of endometrial pathologies. However, these are the only three studies currently, that are indicative of a potential role of TETs in the endometrium and warrants further investigation on its role in endometriosis.…”

“…This data in agreement with other studies, confirming an association between global 5hmC levels and TET expression (Ciesielski et al, ; Du et al, ; Murata et al, ; Putiri et al, ). Other recent studies looking at the involvement of TETs in endometriosis, reported TETs to be downregulated in an ectopic (Roca et al, ) and eutopic (Szczepańska et al, ) endometrial tissues. Despite having a lower TET gene expression, Roca et al () reported high global hydroxymethylation levels in the ectopic endometrium.…”

“…To our knowledge, there are three studies that have investigated TET expression in endometrial pathologies (Ciesielski et al, ; Roca et al, ; Szczepańska, Wirstlein, Zawadzka, Wender‐Ożegowska, & Jagodziński, ). Ciesielski et al (), suggest a discrepancy in TET mRNA levels in endometrial cancer, when compared to normal endometrium.…”

Epigenetic Regulation in Uterine Fibroids—The Role of Ten-Eleven Translocation Enzymes and Their Potential Therapeutic Application

“…Additionally, the importance of demethylation processes and the involvement of TETs in endometrial changes during the menstrual cycle, and impaired expression of TETs in endometrial cancer were described [ 92 , 101 , 102 ]. The expression of TET1 and TET3 was higher in the mid-secretory phase than in the other phases of the endometrial cycle.…”

Endometriosis is associated with an increased whole-blood thrombogenicity detected by a novel automated microchip flow-chamber system (T-TAS®)

“…Despite this, the aetiology of the disorder is still elusive [3]. A growing body of scientific evidence has recently been linking endometriosis with an immunologic dysfunction, metabolic changes, the atherogenic lipid profile, oxidative stress as well as with chronic systemic inflammation [4,5].…”