Aberrant progesterone receptor (PGR) expression is associated with estrogen receptor 1 (ESR1) expression in the...

Estrogen receptor 1 (ESR1) and progesterone receptor (PGR) are essential regulators for endometrial receptivity and embryo implantation. Their expression is dysregulated in women with endometriosis-associated infertility. However, the relationship between ESR1 and PGR within the same endometrial cellular compartments has not been clearly defined. In this study, we examined ESR1 and PGR expression and their correlation in mid-secretory phase eutopic endometrium from fertile women without endometriosis (n = 9) and infertile women with endometriosis (n = 11) using immunohistochemistry and multiplex immunofluorescence. ESR1 levels were significantly reduced in endometrial stromal cells from infertile women with endometriosis compared to controls, and this attenuation of ESR1 was tightly associated with reduced PGR expression. In contrast, although epithelial PGR is normally downregulated in receptive mid-secretory phase endometrium, aberrant epithelial PGR overexpression was strongly correlated with epithelial ESR1 levels in infertile women with endometriosis. Multiplex immunofluorescence and AI-assisted single-cell quantitative analysis further confirmed a significant positive correlation between ESR1 and PGR in both stromal and epithelial compartments in the endometriosis group. These findings reveal compartment-specific dysregulation of ESR1 and PGR expression and identify aberrant ESR1-PGR co-expression as a potential molecular feature of a non-receptive eutopic endometrium in endometriosis-associated infertility, underscoring the importance of disrupted steroid hormone signaling in impaired implantation.