title: Biopsy-induced inflammatory conditions improve endometrial receptivity: the mechanism of action.
abstract: A decade ago, we first reported that endometrial biopsy significantly improves the success of pregnancy in IVF patients with recurrent implantation failure, an observation that was later confirmed by others. Recently, we have demonstrated that this treatment elevated the levels of endometrial pro-inflammatory cytokines and increased the abundance of macrophages (Mac) and dendritic cells (DCs). We therefore hypothesised that the biopsy-related successful pregnancy is secondary to an inflammatory response, and aimed at deciphering its mechanism of action. Supporting our hypothesis, we found that the pro-inflammatory TNFα stimulated primary endometrial stromal cells to express cytokines that attracted monocytes and induced their differentiation into DCs. These monocyte-derived DCs stimulated endometrial epithelial cells to express the adhesive molecule SPP1 (osteopontin (OPN)) and its receptors ITGB3 and CD44, whereas MUC16, which interferes with adhesion, was downregulated. Other implantation-associated genes, such as CHST2, CCL4 (MIP1B) and GROA, were upregulated by monocyte-derived Mac. These findings suggest that uterine receptivity is mediated by the expression of molecules associated with inflammation. Such an inflammatory milieu is not generated in some IVF patients with recurrent implantation failure in the absence of local injury provoked by the biopsy treatment.
authors.affiliation: Department of Biological RegulationThe Weizmann Institute of Science, Rehovot, IsraelIVF UnitDepartment of Obstetric, and Gynecology, Kaplan Medical Center, Rehovot, IsraelDepartment of ObstetricGynecology, Yale University School of Medicine, New Haven, Connecticut, USA yulia.gnainsky@weizmann.ac.il.
authors.forename: Y
authors.initials: Y
authors.lastname: Gnainsky
authors.affiliation: Department of Biological RegulationThe Weizmann Institute of Science, Rehovot, IsraelIVF UnitDepartment of Obstetric, and Gynecology, Kaplan Medical Center, Rehovot, IsraelDepartment of ObstetricGynecology, Yale University School of Medicine, New Haven, Connecticut, USA yulia.gnainsky@weizmann.ac.il.
authors.forename: I
authors.initials: I
authors.lastname: Granot
authors.affiliation: Department of Biological RegulationThe Weizmann Institute of Science, Rehovot, IsraelIVF UnitDepartment of Obstetric, and Gynecology, Kaplan Medical Center, Rehovot, IsraelDepartment of ObstetricGynecology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: P
authors.initials: P
authors.lastname: Aldo
authors.affiliation: Department of Biological RegulationThe Weizmann Institute of Science, Rehovot, IsraelIVF UnitDepartment of Obstetric, and Gynecology, Kaplan Medical Center, Rehovot, IsraelDepartment of ObstetricGynecology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: A
authors.initials: A
authors.lastname: Barash
authors.affiliation: Department of Biological RegulationThe Weizmann Institute of Science, Rehovot, IsraelIVF UnitDepartment of Obstetric, and Gynecology, Kaplan Medical Center, Rehovot, IsraelDepartment of ObstetricGynecology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Or
authors.affiliation: Department of Biological RegulationThe Weizmann Institute of Science, Rehovot, IsraelIVF UnitDepartment of Obstetric, and Gynecology, Kaplan Medical Center, Rehovot, IsraelDepartment of ObstetricGynecology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: G
authors.initials: G
authors.lastname: Mor
authors.affiliation: Department of Biological RegulationThe Weizmann Institute of Science, Rehovot, IsraelIVF UnitDepartment of Obstetric, and Gynecology, Kaplan Medical Center, Rehovot, IsraelDepartment of ObstetricGynecology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: N
authors.initials: N
authors.lastname: Dekel
mesh_terms: D000328:Adult; D001706:Biopsy; D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D010064:Embryo Implantation; D020964:Embryo Loss / Q000276:immunology* / Q000473:pathology; D004622:Embryo, Mammalian / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D004717:Endometrium / Q000166:cytology / Q000276:immunology* / Q000293:injuries*; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D007247:Infertility, Female / Q000276:immunology / Q000517:prevention & control; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells; D055815:Young Adult
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger