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

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dc.contributor.authorHeng, S.
dc.contributor.authorSamarajeewa, N.
dc.contributor.authorAberkane, A.
dc.contributor.authorEssahib, W.
dc.contributor.authorVan de Velde, H.
dc.contributor.authorScelwyn, M.
dc.contributor.authorHull, M.L.
dc.contributor.authorVollenhoven, B.
dc.contributor.authorRombauts, L.J.
dc.contributor.authorNie, G.
dc.date.issued2021
dc.description.abstractObjective: 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).
dc.description.statementofresponsibilitySophea Heng, Nirukshi Samarajeewa, Asma Aberkane, Wafaa Essahib, Hilde Van de Velde, Maxine Scelwyn, Louise Hull, Beverley Vollenhoven, Luk J. Rombauts, and Guiying Nie
dc.identifier.citationFertility and Sterility, 2021; 116(5):1391-1401
dc.identifier.doi10.1016/j.fertnstert.2021.06.028
dc.identifier.issn0015-0282
dc.identifier.issn1556-5653
dc.identifier.orcidHull, M.L. [0000-0003-1813-3971] [0000-0003-4660-4005]
dc.identifier.urihttps://hdl.handle.net/2440/133791
dc.language.isoen
dc.publisherElsevier
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1139568
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1156666
dc.rights©2021 American Society for Reproductive Medicine, Published by Elsevier Inc. This article is available under the Creative Commons CC-BY-NC-ND license and permits non-commercial use of the work as published, without adaptation or alteration provided the work is fully attributed.
dc.source.urihttps://doi.org/10.1016/j.fertnstert.2021.06.028
dc.subjectEndometrial receptivity
dc.subjectIVF
dc.subjectPodocalyxin,
dc.subjectembryo implantation
dc.subjectepithelial receptivity
dc.subject.meshEndometrium
dc.subject.meshCell Line
dc.subject.meshBlastocyst
dc.subject.meshHumans
dc.subject.meshInfertility
dc.subject.meshSialoglycoproteins
dc.subject.meshTreatment Failure
dc.subject.meshEmbryo Transfer
dc.subject.meshFertilization in Vitro
dc.subject.meshEmbryo Culture Techniques
dc.subject.meshPregnancy Rate
dc.subject.meshRetrospective Studies
dc.subject.meshEmbryo Implantation
dc.subject.meshFertility
dc.subject.meshPregnancy
dc.subject.meshVictoria
dc.subject.meshBelgium
dc.subject.meshFemale
dc.titlePodocalyxin inhibits human embryo implantation in vitro and luminal podocalyxin in putative receptive endometrium is associated with implantation failure in fertility treatment
dc.typeJournal article
pubs.publication-statusPublished

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