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Podocalyxin is a key negative regulator of human endometrial epithelial receptivity for embryo implantation

Human Reproduction Apr 12, 2021

Paule SG, Heng S, Samarajeewa N, et al. - Researchers aimed at determining novel adhesion-related membrane proteins with potential roles in receptivity in primary human endometrial epithelial cells (HEECs). Further, they conducted experiments to explore candidates’ in vivo expression pattern in the human endometrium across the menstrual cycle, regulation by progesterone using cell culture, and functional relevance in receptivity employing in vitro human embryo attachment and invasion models. They isolated primary HEECs (n = 9) from the proliferative phase endometrial tissue, combined them into three pools, subjected them to plasma membrane protein enrichment by ultracentrifugation followed by proteomics analysis, which resulted in the discovery of podocalyxin (PCX), a transmembrane protein, as a novel candidate of interest. They performed immunohistochemical analysis to ascertain the in vivo expression pattern and cellular localization of PCX in the human endometrium across the menstrual cycle (n = 23). Outcomes suggest that PCX is a key negative regulator of endometrial epithelial receptivity. In the mid-secretory phase, its specific downregulation in the luminal epithelium, likely mediated by progesterone, may act as a critical step in converting the endometrial surface from a non-receptive to an implantation-permitting state.

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