Receptive window might be shorter in patients with endometriosis and lesions cyclically prepare for implantation.

Objective: To investigate whether endometrial receptivity is affected in patients with endometriosis using podocalyxin (PCX) as a functional biomarker; to study how endometriotic lesions display PCX and the potential pathological implications.

Design: We have previously reported that PCX, an anti-adhesion glycoprotein and barrier protector, is dynamically regulated in the endometrium and acts as a key negative regulator of epithelial receptivity. Early in the cycle both luminal epithelium (LE, lining the endometrial surface) and glandular epithelium (GE, residing within the tissue) strongly express PCX, but in the receptive window PCX is selectively down-regulated in LE, switching the endometrial surface to an adhesive state for embryo attachment/implantation; meanwhile PCX expression is maintained in GE until post-receptivity.

Podocalyxin inhibits human embryo implantation in vitro and luminal podocalyxin in putative receptive endometrium is associated with implantation failure in fertility treatment.

Objective: To study whether endometrial epithelial podocalyxin (PCX) inhibits implantation of human embryos in vitro and in patients undergoing in vitro fertilization (IVF).

Design: We have recently identified PCX as a key negative regulator of endometrial epithelial receptivity. Podocalyxin is expressed in all epithelial cells in the nonreceptive endometrium, but is selectively downregulated in the luminal epithelium (LE) for receptivity.

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

Study Question: How is endometrial epithelial receptivity, particularly adhesiveness, regulated at the luminal epithelial surface for embryo implantation in the human?

Summary Answer: Podocalyxin (PCX), a transmembrane protein, was identified as a key negative regulator of endometrial epithelial receptivity; specific downregulation of PCX in the luminal epithelium in the mid-secretory phase, likely mediated by progesterone, may act as a critical step in converting endometrial surface from a non-receptive to an implantation-permitting state.

What Is Known Already: The human endometrium must undergo major molecular and cellular changes to transform from a non-receptive to a receptive state to accommodate embryo implantation. However, the fundamental mechanisms governing receptivity, particularly at the luminal surface where the embryo first interacts with, are not well understood.