title: A novel role of IGFBP7 in mouse uterus: regulating uterine receptivity through Th1/Th2 lymphocyte balance and decidualization.
abstract: Previously we have screened out Insulin-like Growth Factor Binding Protein 7 (IGFBP7) as a differentially expressed gene in post-implantation uterus versus pre-implantation uterus by suppressive subtractive hybridation. However its function in uterus was not clearly identified. In this research, the expression and function of IGFBP7 during post-implantation were studied. We found that IGFBP7 was mainly located in the glandular epithelium and the stroma, and was upregulated after embryo implantation. The vector pCR3.1-IGFBP7-t expressing partial IGFBP7 was constructed. Inhibition of IGFBP7 by specific DNA immunization induced significant reduction of implanted embryos and pregnancy rate. The number of implanted embryos (5.68 ± 0.46) was significantly reduced after immunization with pCR3.1-IGFBP7-t, as compared with that of the mice immunized with the control vector (12.29 ± 0.36) or saline (14.58 ± 0.40) (p<0.01). After specific inhibition of IGFBP7, the T helper type 1 (Th1) cytokine IFNγ, was significantly elevated (p<0.05) and the Th2 cytokines IL-4 and IL-10, were reduced in uteri (p<0.05). The increase of Tbet and the decrease of Gata3 were found in mice peripheral lymphocytes by flow cytometry. The expression of decidualization marker IGFBP1 and angiogenesis regulator VEGF were declined in uteri (p<0.05). The expression of apoptosis-associated proteins, caspase3 and Bcl-2, were also declined (p<0.05). These results showed that inhibition of IGFBP7 induced pregnancy failure by shifting uterine cytokines to Th1 type dominance and repressing uterine decidualization.
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Zhen-Kun
authors.initials: ZK
authors.lastname: Liu
authors.forename: Rong-Chun
authors.initials: RC
authors.lastname: Wang
authors.forename: Bing-Chen
authors.initials: BC
authors.lastname: Han
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.forename: Jing-Pian
authors.initials: JP
authors.lastname: Peng
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000235:genetics / Q000276:immunology; D003656:Decidua / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism; D010064:Embryo Implantation; D004848:Epithelium / Q000378:metabolism; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000276:immunology; D018507:Gene Expression Regulation, Developmental; D005822:Genetic Vectors; D007114:Immunization; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics / Q000276:immunology; D018969:Insulin-Like Growth Factor Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D051379:Mice; D011247:Pregnancy; D011270:Pregnancy, Animal; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000276:immunology; D058408:Th1-Th2 Balance; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000276:immunology
chemical_list: D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; C556062:IL10 protein, mouse; D018970:Insulin-Like Growth Factor Binding Protein 1; D018969:Insulin-Like Growth Factor Binding Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019444:Vaccines, DNA; D042461:Vascular Endothelial Growth Factor A; C102529:insulin-like growth factor binding protein-related protein 1; C467480:vascular endothelial growth factor A, mouse; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; C505409:Casp3 protein, mouse; D053148:Caspase 3