Aberrant Expression of Estrogen Receptor alpha is Strongly Associated with Progesterone Receptor in the Endometrium from Infertile Women with Endometriosis

Abstract Text Estrogen receptors (ESRs) and progesterone receptor (PGR) are nuclear receptors that regulate signaling pathways in the endometrium that are critical for endometrial receptivity and the establishment of pregnancy. Endometriosis is a chronic condition characterized by the growth of endometrial tissue outside the uterine cavity, leading to infertility and pelvic pain. The main factor in the pathology of endometriosis is the dysregulation of steroid hormone signaling. It has been suggested that abnormal expression of ESR1 and PGR contributes to aberrant steroid hormone responsiveness in endometriosis. In this study, we show a positive correlation between ESR1 and PGR in human endometrium from infertile women with endometriosis. We assessed levels of ESR1 and PGR in the endometrium from secretory phase infertile women with endometriosis along with control women without endometriosis. The levels of ESR1 were significantly reduced in human endometrial stromal cells from infertile women with endometriosis compared to women without endometriosis. This attenuation of ESR1 was tightly associated with PGR in endometrial stromal cells. Although the levels of ESR1 in endometrial epithelial cells were not different between control and infertile women with endometriosis, there is a positive correlation between ESR1 and PGR in human endometrial epithelial cells. Epithelial expression of PGR should be down regulated at receptive endometrium at mid-secretory phase in human. However, aberrant overexpression of PGR was tightly associated to ESR1 levels in epithelial cells from infertile women with endometriosis. Furthermore, our multiplex immunofluorescence assays and quantitative analysis revealed that ESR1 expression positively correlated with PGR expression in human endometrium. Taken together, our results support a tight regulation of ESR1 and PGR for receptive endometrium and demonstrate aberrant dysregulation of ESR1 and PGR in human endometrium from infertile women with endometriosis. Our findings support the fact that tight regulation of ESR1 and PGR is critical for receptive endometrium. We suggest that ESR1 regulates PGR expression, providing a potential mechanism of aberrant PGR overexpression in epithelial cells of nonreceptive endometrium in endometriosis-associated infertility. Date of Presentation October 16, 2024