Estrogen receptor splice variants may be associated with endometriosis pathogenesis and clinical severity.

Estrogen splice variants and their implication in endometriosis

Key Points

Highlights:

• Estrogen receptor splice variants may be associated with endometriosis pathogenesis and clinical severity of pain.

Importance:

• Understanding the complex genetic etiology of endometriosis may allow researchers to develop targeted pharmacologic treatments against this disease.

Key Points:

• In this study, 30 women with endometriosis and 28 women without endometriosis were evaluated for estrogen receptor alpha splice variants and any association 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).
• In the proliferative phase of the endometrium, the ratio between ERα and ERα del.4 (P = 0.032), and ERα/del.7 (P = 0.027) were significantly higher in women with endometriosis than in the control group.
• No significant difference in the expression of wt-ERα was seen in the endometrium of women with and without endometriosis.

Lay Summary

Endometriosis is defined as the presence of uterine stroma and glands outside of the uterine cavity and is one of the leading causes of chronic pelvic pain in women. Thus, understanding key genetic markers of this disease and evaluating those with the risk of progression is a key aim of current research. Estrogen receptors and their variants have been seen to be an important player in the pathogenesis of endometriosis. Briefly, there are two main forms of estrogen receptors. Estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) which are both involved in a wide array of biological processes such as normal cell growth. If these receptors are mutated or changed in such a way that brings about their increased activity, unregulated growth of cells can ensue. ERα splice variants have recently been implicated in the dysregulation of growth in estrogen-responsive tissues such as the endometrium of the uterus. This study aims to understand which ERα slice variants are associated with endometriosis and their relative expression in endometrial tissue.

30 women with endometriosis and 28 women without endometriosis with a mean age of 34.93 ± 9.25 and 38.75 ± 8.35 years, respectively, were recruited into the study. Endometrial tissue obtained from these women were then analyzed by Q-PCR for expression of ERα variants. They found that (wild-type, non-mutated) wt-ERα and all four splice variants of ERα were expressed in the endometrium of women with and without endometriosis, regardless of the stage of their menstrual cycle. The endometrium of women with endometriosis had decreased levels of ERα variants Del.4 (P = 0.047) and Del.7 (P = 0.032) compared to the healthy endometrium. No significant difference in the expression of wt-ERα was seen in the endometrium of women with and without endometriosis. In the proliferative phase of the endometrium, the ratio between ERα and ERα del.4 (P = 0.032), and ERα/del.7 (P = 0.027) were significantly higher in women with endometriosis than in the control group.

This study addresses the complexity of estrogen receptor modifications and variations that can occur in both healthy and aberrant endometrial tissues. However, further studies are warranted to further investigate the findings presented in this study.

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/29299139