title: [Relationship between the expression of chemokines and their receptors in the maternal-fetal interface and pathogenesis of unexplained recurrent spontaneous abortion].
abstract: OBJECTIVE
  To explore the relationship between the expression of chemokines and their receptors in the maternal-fetal interface and the pathogenesis of unexplained recurrent spontaneous abortion (URSA).
  
  
  METHODS
  8-10 weeks CBA/J female mice were mated with DBA/2 and BALB/c male mice at the ratio of 2:1 to establish the model of normal pregnant mice (CBA/J × BALB/c) and URSA mice (CBA/J × DBA/2). Sixty mice were divided into 6 groups, with ten in each group. The mice in the normal unpregnancy group were executed for endometrial tissues; the mice in the embryonic implantation normal pregnancy group were executed for endometrial tissues at the sixth day of gestation; the mice in the embryonic development normal pregnancy group were executed for decidua and chorionic tissues at the fourteenth day of gestation. While, the mice in the embryonic implantation URSA group were executed for endometrial tissues at the sixth day of gestation; the mice in the pre-abortion URSA group were executed for decidua and chorionic tissues at the ninth day of gestation; the mice in the post-abortion URSA group were executed for decidua and chorionic tissues at the fourteenth day of gestation. The chemokines and their receptors in different tissues of the mice were determined by western blot, including the protein expression of stromal cell derived factor (CXCL12), monocyte chemotactic protein 1 (CCL2), regulated upon activation normal T cell expressed and secreted (RANTES) and their receptor CXCR4, CCR2, CCR5 in maternal-fetal interface.
  
  
  RESULTS
  (1) The protein expression of CXCL12 and CXCR4, CCL2 and CCR2, RANTES and CCR5 in endometrial tissues of the normal unpregnant group were 0.13 ± 0.04 and 0.18 ± 0.09, 0.057 ± 0.023 and 0.39 ± 0.08, 0.034 ± 0.012 and 0.22 ± 0.05, respectively. They were 0.35 ± 0.09 and 0.93 ± 0.15, 0.349 ± 0.056 and 0.91 ± 0.15, 0.336 ± 0.089 and 0.44 ± 0.05 in endometrial tissues in the embryonic implantation normal pregnancy group; and were 0.62 ± 0.15 and 1.23 ± 0.28, 0.283 ± 0.051 and 0.55 ± 0.09, 0.225 ± 0.065 and 0.35 ± 0.07 in decidua tissues in the embryonic development normal pregnancy group. The protein expression of chemokines and their receptors in endometrial tissues in the embryonic implantation normal pregnancy group and in decidua tissues in the embryonic development normal pregnancy group were higher than those in the normal unpregnancy group, with statistically significant difference (P < 0.05). Compared with the embryonic implantation normal pregnancy group, CXCL12 and CXCR4 in decidual tissues in the embryonic development normal pregnancy group were significantly higher (P < 0.05), while CCL2 and CCR2, RANTES and CCR5 were significantly lower (P < 0.05). (2) Compared with the embryonic implantation normal pregnancy group, CXCL12 and CXCR4 (0.20 ± 0.06 and 0.44 ± 0.11) in endometrial tissues in the embryonic implantation URSA group were significantly lower (P < 0.01), while CCL2 and CCR2 (0.451 ± 0.133 and 1.32 ± 0.20), RANTES and CCR5 (0.488 ± 0.137 and 0.61 ± 0.18) were higher (P < 0.05). (3) Compared with the embryonic development normal pregnancy group, CXCL12 and CXCR4 in decidual tissues of pre-abortion URSA group (0.27 ± 0.09 and 0.26 ± 0.10), post-abortion URSA group (0.25 ± 0.08 and 0.23 ± 0.08) were significantly lower (P < 0.01), while CCL2 and CCR2 (0.576 ± 0.123 and 0.92 ± 0.15 in the pre-abortion URSA group; 0.748 ± 0.112 and 1.56 ± 0.34 in the post-abortion URSA group), RANTES and CCR5 (0.294 ± 0.054 and 0.59 ± 0.18 in the pre-abortion URSA group; 0.363 ± 0.058 and 0.78 ± 0.14 in the post-abortion URSA group) were significantly higher (P < 0.05). CCL2 and CCR2, RANTES and CCR5 in decidual tissues in the post-abortion URSA group was obviously higher than those of the pre-abortion URSA group, with statistically significant difference (P < 0.05).
  
  
  CONCLUSIONS
  The accurate expression of CXCL12, CCL2, RANTES and their receptors CXCR4, CCR2, CCR5 play important roles in the embryonic implantation and development. The lower expression of CXCL12 and CXCR4 protein and higher expression of CCL2 and CCR2, RANTES and CCR5 in decidua and chorionic tissues are closely related to the pathogenesis of URSA.
authors.affiliation: Department of Family Planning, the Second Hospital of Tianjin Medical University, Tianjin 300211, China; Email: xiaoxiaozhang2006@126.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Family Planning, the Second Hospital of Tianjin Medical University, Tianjin 300211, China.
authors.forename: Jianmei
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Family Planning, the Second Hospital of Tianjin Medical University, Tianjin 300211, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Family Planning, the Second Hospital of Tianjin Medical University, Tianjin 300211, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
mesh_terms: D000026:Abortion, Habitual / Q000378:metabolism; D000022:Abortion, Spontaneous / Q000378:metabolism*; D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism*; D054377:Chemokine CXCL12 / Q000378:metabolism*; D003656:Decidua / Q000378:metabolism*; D010064:Embryo Implantation; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D011247:Pregnancy; D019718:Receptors, CXCR4 / Q000378:metabolism*; D017154:Stromal Cells
chemical_list: C111835:CCL2 protein, human; C515255:CXCL12 protein, human; D018932:Chemokine CCL2; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4