Correlation Between Progesterone Receptor Isoforms and Endometrial Stem Cell Markers in PCOS-Associated Infertility

Abstract

Progesterone receptor isoforms, PRA and PRB, are critical for regulating endometrial decidualization and
maintaining receptivity during the implantation window. In women with polycystic ovary syndrome
(PCOS), dysregulation of these receptors can result in progesterone resistance and endometrial
dysfunction, contributing to infertility. This study aimed to quantify the expression levels of progesterone
receptor isoforms (PRA and PRB), evaluate the expression of stem cell markers (Nanog, Sox, and c-Myc),
and explore the correlation between PR isoforms and stem cell markers in endometrial samples from
women with PCOS compared to healthy controls. A case–control study was conducted involving 100
participants, including 50 women with PCOS and 50 non-PCOS controls. Endometrial tissue was collected
and analysed using flow cytometry and quantitative PCR to assess receptor and marker expression.
Statistical analyses, including t-tests, Pearson correlation, and regression models, were performed to
determine group differences and associations. Women with PCOS exhibited significantly higher PRA and
PRB expression levels, accompanied by elevated stem cell marker expression (p < 0.001). Strong positive
correlations were found between PR isoforms and stemness markers, indicating a mechanistic link between
hormonal dysregulation and increased endometrial stem cell activity. The findings suggest that altered PR
signaling and enhanced stem cell activity underlie progesterone resistance and impaired endometrial
receptivity in PCOS. These insights provide a basis for developing targeted therapeutic interventions, such
as selective PR modulators and regulators of stem cell pathways, to improve fertility outcomes in affected
women.