title: Chemokine Receptor Type 4 Regulates Migration and Invasion of Trophectoderm Cell in the Human Blastocyst.
abstract: Chemokine receptor type 4 (CXCR4) has been suggested to regulate cell migration and invasion in human somatic cells. However, its role in human oocytes and embryos has not been investigated directly. Here we show that CXCR4 mRNA was initially expressed at the 4-cell stage, and its expression gradually increased until the blastocyst stage, whereas its protein was detectable only after the 8-cell stage. In addition, CXCR4 mRNA and protein were expressed in the inner cell mass (ICM) and trophectoderm (TE) cell of the blastocyst. Furthermore, we collected embryos from women whose embryos had undergone successful implantation (SI) and those whose embryos had failed implantation (FI) in their fresh cycles. TE cells from the FI group had reduced CXCR4 mRNA expression relative to those from the SI group but not in the ICM. Through ICM replacement, we constructed mouse blastocysts in which Cxcr4 was specifically knocked down in TE cells to simulate the CXCR4 expression profile of human blastocysts from the FI group. In this case, we found that the implantation rate significantly decreased after transfer of reconstructed embryos. Bioinformatic analysis indicated that CXCR4 can induce cell apoptosis and migration mediated by Rho signaling. This hypothesis was confirmed by invasion and migration experiments, using a human trophoblast cell line. The present study is the first to explore the characteristics of CXCR4 expression using human oocytes and embryos and suggests that CXCR4 is required upstream of TE cell apoptosis and migration. CXCR4 expression is a potential biomarker to predict implantation competence during assisted reproductive technologies.
authors.affiliation: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, China Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China.
authors.forename: Siyu
authors.initials: S
authors.lastname: Bao
authors.affiliation: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, China Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China.
authors.forename: Tianjie
authors.initials: T
authors.lastname: Li
authors.affiliation: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, China Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Long
authors.affiliation: Yunnan Key Laboratory of Primate Biomedical Research, and Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan Province, China.
authors.forename: Jinjuan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, China Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China.
authors.forename: Hongcui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, China Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, China Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.affiliation: Yunnan Key Laboratory of Primate Biomedical Research, and Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan Province, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Tan
authors.affiliation: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, China Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China yuyang5012@hotmail.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, China Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China jie.qiao@263.net.
authors.forename: Jie
authors.initials: J
authors.lastname: Qiao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001755:Blastocyst / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D010064:Embryo Implantation / Q000502:physiology*; D005307:Fertilization in Vitro; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014327:Trophoblasts / Q000378:metabolism*
chemical_list: C527276:CXCR4 protein, human; D019718:Receptors, CXCR4
keywords: CXCR4; Rho signaling pathway; human fertilized embryo; implantation; trophectoderm cell