Excerpt
Endometriosis is defined as the presence of endometrial tissue outside the uterus, predominantly on the ovary and pelvic peritoneum [
1]. It occurs in approximately 10 % of women of reproductive age and, although it is a benign disease, it causes infertility and pelvic pain, compromising the quality of life [
1]. Out of various theories put forward to explain the origin of endometriosis, retrograde menstrual reflux has gained the widest acceptance [
1,
2]. Endometriosis has been reported to be characterized by the presence of endometrial cells with capacity to avoid apoptosis beyond the uterine cavity [
1,
2]. Apoptosis plays an important role in maintaining tissue homeostasis by striking a balance between proliferation and cell death [
1]. Endometriotic cells have been described to show the peculiar biological characteristics of resistance to apoptosis with the inability to transmit apoptotic signal and the ability to avoid cell death [
1,
2]. Recently, endometriosis has been correlated with aberrant endometrial expression of telomerase and survivin implying modifications in cell fate [
1,
2]. Telomerase is a specialized transcriptase that can prevent telomere shortening [
2,
3]. Telomeres are non-coding tandemly repeated DNA sequences that are vital for maintaining chromosomal integrity and cell stability [
2]. The critical shortening of telomeres is linked to cell division and their senescence and death [
2,
3]. Consequently, telomerase activation allows cells to overcome apoptosis acquiring immortal capacity [
2,
3]. Survivin is the smallest member of the inhibitor of apoptosis protein family that acts by suppressing primarily caspases [
1,
4]. It is prominently expressed in embryonic and fetal tissues and over-expressed in virtually all tumor types [
1]. It is transcriptionally silent in most differentiated adult tissues, but it is expressed in ovary and in the proliferative phase of the cycling human endometrium, suggesting a physiological role in normal endometrial function [
1,
4]. Survivin has been shown to be closely linked to escape from apoptosis of endometriotic cells and their viability with a critical role in the pathogenesis and progression of endometriosis together with telomerase [
1‐
4]. It has been found that both the survivin and telomerase are up-regulated by epidermal growth factor (EGF) through MAPK (mitogen activated protein kinase) signaling pathway activation [
3,
4]. MAPK has been reported to play an important role in many cellular reactions such as apoptosis, proliferation and inflammation [
5]. Many studies have demonstrated that MAPK is involved directly in regulating the pathogenesis of endometriosis [
5]. MAPK pathways seem to play a pivotal role as intracellular and extracellular signal transducers in endometriotic cells [
6,
7]. It has been reported that enhanced proliferation and survival of eutopic endometrial cells from patients with endometriosis compared with healthy women have correlated with abnormal activation of MAPK signaling pathways [
7]. In addition, accumulating evidences, show that MAPK pathways regulate pain hypersensitivity in different injury conditions implying their possible involvement in endometriosis-related pelvic pain [
8]. With respect to the above, we suggest that inhibition of MAPK signaling pathway down-regulating both telomerase and survivin expression, may be candidate as a new therapeutic target for endometriosis. Moreover, understanding the possible regulatory role of MAPK in apoptosis and, ultimately, in the signal transduction pathway among telomerase, survivin and EGF may help us to better define the intricate endometriosis pathological etiology. …
