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

Abstract

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. In the current study, we first investigated whether high levels of PCX in Ishikawa monolayer inhibit attachment and/or penetration of human blastocysts in in vitro models. We then examined PCX by immunohistochemistry in putative receptive endometrial tissues biopsied from 81 IVF patients who underwent frozen embryo transfer in the next natural cycle and retrospectively analyzed the association between PCX staining in LE and clinical pregnancy as a proxy of successful implantation. Setting: RMIT University, Australia; Vrije Universiteit Brussel, Belgium. Patient(s): In vitro fertilization patients undergoing frozen/thawed embryo transfer. Intervention(s): N/A. Main Outcome Measure(s): Endometrial epithelial PCX inhibits implantation of human embryos in vitro and in IVF patients. Result(s): High levels of PCX in Ishikawa monolayer significantly inhibited blastocyst attachment and penetration. Among the 81 putative receptive tissues, 73% were negative, but 27% were heterogeneously positive for PCX in LE. The clinical pregnancy rate was 53% in those with a PCX-negative LE but only 18% in those with a PCX-positive LE. If LE was positive for PCX, the odds ratio of no clinical pregnancy was 4.95 (95% Confidence interval, 1.48–14.63).