Reduced alternative splicing of estrogen receptor alpha in the endometrium of women with endometriosis

Endometriosis is a condition which involves the presence of uterine stroma and glands outside of the uterine cavity and represents one of the most prevalent disorders of the female reproductive tract. The key symptom of endometriosis is pain, including dysmenorrhea, deep dyspareunia, and chronic pelvic pain. As such, endometriosis has significant economic consequences within the healthcare system and can influence the daily quality of life in affected patients. However, the pathophysiology of this disease and the mechanisms in which this condition generates pain are very unclear. This study, involving 30 women with endometriosis and 28 controls without endometriosis, aimed to investigate relative levels of estrogen receptor alpha (ERα) splice variants in the endometrium of women with and without endometriosis and investigate potential links to the severity of pain. Wild type (wt)-ERα was dominantly expressed in human endometrium while the expression of ERα-del.4, ERα-del.7, and ERα-del.3,4 was significantly reduced in endometriosis patients compared with healthy patients (p < 0.05). Furthermore, the relative ratios of wtERα:ERα-del.4, and wtERα:ERα-del.3,4 were associated with the severity of pain in endometriosis patients (p < 0.05). Consequently, analyzing differences in the relative levels of four types of ERα splice variant in the endometrium of patients with endometriosis may help in the development of endometriosis-targeted treatment and the development of appropriate therapies.