Human trophectoderm apposition is regulated by interferon γ-induced protein 10 (IP-10) during early implantation

• Published in: Placenta (Eastbourne) Vol. 34; no. 3; pp. 222 - 230
• Main Authors: Sela, H.Y, Goldman-Wohl, D.S, Haimov-Kochman, R, Greenfield, C, Natanson-Yaron, S, Hamani, Y, Revel, A, Lavy, Y, Singer, O, Yachimovich-Cohen, N, Turetsky, T, Mandelboim, O, Reubinoff, B, Yagel, S
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01-03-2013; Elsevier
• Subjects: Adult; Biological and medical sciences; Blastocyst attraction; Cell Movement - drug effects; Cells, Cultured; Chemokine CXCL10 - pharmacology; Chemokines; Chemotaxis - drug effects; Chorionic Villi - physiology; Culture Techniques; Ectoderm - drug effects; Ectoderm - metabolism; Embryo Implantation - physiology; Embryology: invertebrates and vertebrates. Teratology; Endometrium; Endometrium - cytology; Endometrium - metabolism; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental - drug effects; Humans; Internal Medicine; IP-10; Obstetrics and Gynecology; Pregnancy; Pregnancy Trimester, First; Receptors, CXCR3 - genetics; Receptors, CXCR3 - metabolism; Stromal Cells - cytology; Stromal Cells - metabolism; Trophectoderm; Trophoblasts - drug effects; Trophoblasts - metabolism; Blastocyst attraction; Trophectoderm; IP-10; Chemokines; Endometrium; Pregnancy; Human; Vertebrata; Regulation(control); Mammalia; Ovum implantation; Early; Protein; Gamma interferon
• ISSN: 0143-4004; 1532-3102
• DOI: 10.1016/j.placenta.2012.12.008

Abstract Introduction The first step in human implantation is the attraction of the blastocyst to the endometrium. We aimed to study attraction of the human blastocyst to the endometrium, and how this process is accomplished by chemokines secreted by the endometrium. Materials and methods Blastocyst trophectoderm cells and other trophoblast lineage cells were subjected to attraction assays by IP-10 and other chemokines using transwell migration and chemotaxis assays. Chemokine expression and secretion were investigated using immunohistochemistry, ELISA, FACS analysis, and RT-PCR on material from flushing of the uterine cavity in endometrial biopsies. Chemokine receptor expression by blastocyst trophectoderm following PGD biopsy, trophectoderm derived from hES, placental villi, and other trophoblast lineage cells were characterized by the same methods. Results IP-10 dramatically attracted trophectoderm derived from hES cells and other lineages by interaction with CXCR3 chemokine receptors, as shown by both chemotaxis and transwell migration. High levels of IP-10 were detected throughout the menstrual cycle at flushing of the uterine cavity. Immunohistochemistry, FACS analysis, and RT-PCR of endometrial biopsy detected IP-10 in glandular and stromal cells of the endometrium. High levels of IP-10 were detected in condition medium of the endometrial stromal and glandular cells. Of all of the chemokine/chemokine receptor combinations examined, the IP-10/CXCR3 interaction was the only cytokine that was significantly elevated. Discussion While they await the wandering blastocyst, IP-10 is produced by many cells of the endometrium, but not by endometrial natural killer cells. Conclusion Endometrial IP-10 may specifically attract human blastocyst trophectoderm cells early in implantation.