title: CXCL12 controls over-invasion of trophoblasts via upregulating CD82 expression in DSCs at maternal-fetal interface of human early pregnancy in a paracrine manner.
abstract: Tetraspanin CD82 has been identified as a potential contributor to controlling trophoblast invasiveness in human first-trimester pregnancy. However, it is unclear how the regulation of CD82 expression at maternal-fetal interface. The present study is to investigate the effect of the trophoblast-derived CXCL12 on CD82 expression in decidual stromal cells (DSCs) that in turn controls trophoblast cell invasiveness. In-cell Western was used to evaluate the expression of CD82 in DSCs. A co-culture model was established to investigate the reciprocal interaction between trophoblasts and DSCs via CXCL12/CXCR4 and CD82 expression. We found that both anti-CXCL12 and anti-CXCR4 neutralizing antibody can eliminate increase of CD82 expression in DSCs induced by the trophoblasts supernatant. Moreover, the invasiveness of trophoblasts pre-treated with anti-CXCR4 neutralizing antibody was significantly decreased. Interestingly, when DSCs were pre-treated with anti-CXCR4 neutralizing antibody, the trophoblasts invasiveness in the co-culture was enhanced, and thus anti-CXCR4 neutralizing antibody can reverse the decrease of trophoblasts invasiveness induced by CD82. The trophoblast cell-derived CXCL12 does not only increase the invasiveness in an autocrine manner, but also control the over-invasion of trophoblasts through promoting CD82 expression in DSCs in a paracrine manner, which maintains a physiological balance of human trophoblasts invasiveness via the cross-talk between trophoblasts and DSCs.
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, 200011, China.
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Li
authors.forename: Chuan-Lin
authors.initials: CL
authors.lastname: Tang
authors.forename: Mei-Rong
authors.initials: MR
authors.lastname: Du
authors.forename: Deng-Xuan
authors.initials: DX
authors.lastname: Fan
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Zhao
authors.forename: Bing
authors.initials: B
authors.lastname: Xu
authors.forename: Da-Jin
authors.initials: DJ
authors.lastname: Li
mesh_terms: D057134:Antibodies, Neutralizing; D015153:Blotting, Western; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism*; D018920:Coculture Techniques; D003656:Decidua / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006801:Humans; D051861:Kangai-1 Protein / Q000378:metabolism*; D008431:Maternal-Fetal Exchange / Q000502:physiology; D019899:Paracrine Communication / Q000502:physiology*; D010920:Placenta / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism*
chemical_list: D057134:Antibodies, Neutralizing; C497688:CD82 protein, human; D054377:Chemokine CXCL12; D051861:Kangai-1 Protein