Expression of Membrane Progesterone Receptors in Eutopic and Ectopic Endometrium of Women with Endometriosis

Abstract

Endometriosis is one of the most frequent gynecological diseases in reproductive age women, but its etiology is not completely understood. Endometriosis is characterized by progesterone resistance, which has been explained in part by a decrease in the expression of the intracellular progesterone receptor in the ectopic endometrium. Progesterone action is also mediated by nongenomic mechanisms via membrane progesterone receptors (mPRs) that belong to the class II members of the progesterone and adipoQ receptor (PAQR) family. The aim of the present study was to evaluate the expression at mRNA and protein levels of mPR members in the eutopic and ectopic endometrium of women with endometriosis. Total RNA and total protein were isolated from control endometrium (17 samples), eutopic endometrium (17 samples), and ectopic endometrium (9 samples). The expression of PAQR7 (mPRα), PAQR8 (mPRβ), and PAQR6 (mPRδ) at mRNA and protein levels was evaluated by RT-qPCR and Western blot, whereas PAQR5 (mPRγ) gene expression was evaluated by RT-qPCR. Statistical analysis between comparable groups was performed using one-way ANOVA followed by Tukey’s multiple comparisons test with a confidence interval of 95 %. The analysis of gene expression showed that PAQR7 and PAQR5 expression was lower in both eutopic and ectopic endometrium as compared to the endometrium of women without endometriosis, whereas the expression of PAQR8 and PAQR6 was only reduced in eutopic endometrium. Furthermore, mPRα and mPRβ protein content was decreased in the ectopic endometrium of women with endometriosis. Our results demonstrate a decrease in the expression and protein content of mPRs in eutopic and ectopic endometrium of patients with endometriosis, which could contribute to the progesterone resistance observed in patients with this disease.

Functional Implications of Estrogen and Progesterone Receptors Expression in Adenomyosis, Potential Targets for Endocrinological Therapy

“…In contrast to endometrial cancer [ 44 ] and endometriotic tissues [ 45 ] we did not observe decreased expression of progesterone membrane receptors in adenomyosis. Previous studies have shown that the mPRα and mPRβ expression at gene as well as protein levels was significantly downregulated in the ectopic endometrium of patients with endometriosis compared to the endometrium of healthy women [ 45 ].…”

“…In contrast to endometrial cancer [ 44 ] and endometriotic tissues [ 45 ] we did not observe decreased expression of progesterone membrane receptors in adenomyosis. Previous studies have shown that the mPRα and mPRβ expression at gene as well as protein levels was significantly downregulated in the ectopic endometrium of patients with endometriosis compared to the endometrium of healthy women [ 45 ]. We detected strong expression of mPRβ both in the stromal cells and the glandular epithelium, as well as mPRα and mPRγ, mainly in the cytoplasm of the glandular tissue, suggesting that adenomyosis is a separate disease, and may express molecular differences compared to endometriosis.…”

MicroRNAs and Progesterone Receptor Signaling in Endometriosis Pathophysiology

“…mPRα and mPRβ were localized primarily to cell membranes, while mPRγ was localized in the cytoplasm and/or nucleus of normal endometrial tissue, while mPRα and mPRβ were detected at the cell membrane or in the cytoplasm, or both, while mPRγ was only localized in the cytoplasm of endometrial cancer tissue [ 37 ]. Within the context of endometriosis, mPRs expression was recently reported for both transcript and protein [ 38 ]. mPRα and mPRγ transcript expression ( PAQR7 and PAQR8 , respectively) were both lower in eutopic endometrium and ectopic lesion tissue compared to control endometrial tissue, while transcript expression of mPRβ ( PAQR8 ) and mPRδ ( PAQR6 ) was only reduced in the eutopic endometrium, with lesion tissue expressing similar levels to that of the control endometrium.…”

What Do We Know about Classical and Non-Classical Progesterone Receptors in the Human Female Reproductive Tract? A Review

“…Additionally, reduced PGRMC2, mPRα, mPRβ, and mPRγ expression has been observed in endometrial hyperplasia and endometriosis [ 11 , 162 , 163 ]. This finding confirms the role of PGRMC2 up-regulation in the secretory phase and how P4 acts through these receptors to inhibit cell proliferation.…”