title: HCG-Activated Human Peripheral Blood Mononuclear Cells (PBMC) Promote Trophoblast Cell Invasion.
abstract: Successful embryo implantation and placentation depend on appropriate trophoblast invasion into the maternal endometrial stroma. Human chorionic gonadotropin (hCG) is one of the earliest embryo-derived secreted signals in the peripheral blood mononuclear cells (PBMC) that abundantly expresses hCG receptors. The aims of this study were to estimate the effect of human embryo-secreted hCG on PBMC function and investigate the role and underlying mechanisms of activated PBMC in trophoblast invasion. Blood samples were collected from women undergoing benign gynecological surgery during the mid-secretory phase. PBMC were isolated and stimulated with or without hCG for 0 or 24 h. Interleukin-1β (IL-1β) and leukemia inhibitory factor (LIF) expressions in PBMC were detected by enzyme-linked immunosorbent assay and real-time polymerase chain reaction (PCR). The JAR cell line served as a model for trophoblast cells and was divided into four groups: control, hCG only, PBMC only, and PBMC with hCG. JAR cell invasive and proliferative abilities were detected by trans-well and CCK8 assays and matrix metalloproteinase (MMP)-2 (MMP-2), MMP-9, vascular endothelial growth factor (VEGF), tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 expressions in JAR cells were detected by western blotting and real-time PCR analysis. We found that hCG can remarkably promote IL-1β and LIF promotion in PBMC after 24-h culture. PBMC activated by hCG significantly increased the number of invasive JAR cells in an invasion assay without affecting proliferation, and hCG-activated PBMC significantly increased MMP-2, MMP-9, and VEGF and decreased TIMP-1 and TIMP-2 expressions in JAR cells in a dose-dependent manner. This study demonstrated that hCG stimulates cytokine secretion in human PBMC and could stimulate trophoblast invasion.
authors.affiliation: Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China; Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Nan
authors.initials: N
authors.lastname: Yu
authors.affiliation: Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Yan
authors.affiliation: Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
authors.forename: Tailang
authors.initials: T
authors.lastname: Yin
authors.affiliation: Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
authors.forename: Danni
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
authors.forename: Mei
authors.initials: M
authors.lastname: Xu
authors.affiliation: Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
authors.forename: Jinli
authors.initials: J
authors.lastname: Ding
authors.affiliation: Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D010064:Embryo Implantation / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics; D053605:Leukemia Inhibitory Factor / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology* / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D006063:Chorionic Gonadotropin; D053583:Interleukin-1beta; D053605:Leukemia Inhibitory Factor; D019715:Tissue Inhibitor of Metalloproteinase-1; D042461:Vascular Endothelial Growth Factor A; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9