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

Abstract

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.

An assessment of the multifactorial profile of steroid-metabolizing enzymes and steroid receptors in the eutopic endometrium during moderate to severe ovarian endometriosis

“…For estrogen, two structurally related ER subtypes, ERα and ERβ – which are products of two separate genes – signal when complexed with E2. Although the involvement of the ER subtypes (ERα and ERβ) in the progression of endometriosis is not clear [67, 68], the results obtained from the present study of North Indian women concur with the findings reported by Zhang et al (2018), who also did not observe any change in the levels of the wild type ERα mRNA in a population of fertile Chinese women with and without endometriosis [69].…”

CYP19A1 May Influence Lambing Traits in Goats by Regulating the Biological Function of Granulosa Cells

“…Follicular granulosa cells are thus of great significance to the success of early gestation. Aromatase, isolated from the placenta in 1988 [ 9 , 10 ], belongs to the cytochrome P450 family and is responsible for the conversion of androstenedione (A2), testosterone (T), and 16a-hydroxyandrostenediol into estrone (E1), oestradiol (E2), and estriol (E3), respectively. Zhang et al proposed that CYP19A1 is a vital enzyme in estrogen synthesis and plays an important role in establishing and maintaining pregnancy [ 11 ].…”

Estrogen receptor alpha isoform ERdelta7 in myometrium modulates uterine quiescence during pregnancy

“…In humans, ERΔ7 mRNA has been detected in the brain, breast and uterus as well as endocrine tumors. [[19], [20], [21], [22], [23]] Importantly ERΔ7 has been previously demonstrated to bind the DNA binding domain (DBD) and heterodimerize with other ERα isoforms acting in a dominant negative manner limiting ERα action [24].…”