title: Blockade of adhesion molecule CD146 causes pregnancy failure in mice.
abstract: Unexplained pregnancy loss and recurrent miscarriage seriously impair human fecundity. However, the underlying molecular mechanisms remain elusive. Recent studies suggest that the adhesion molecule CD146 may be involved in unexplained recurrent miscarriage. Here, we investigate the effect of CD146 on early pregnancy. Using in situ hybridization and immunohistochemistry, we found that CD146 was specifically expressed in the receptive maternal uteri and invasive embryonic trophoblasts during the early stages of pregnancy, but it was completely absent in the non-pregnant uterus. Our in vitro studies demonstrated that blocking CD146 with a function-perturbation antibody AA98 significantly inhibited the attachment of blastocysts onto the receptive uterine luminal epithelial monolayer, the trophoblastic outgrowth of blastocysts and ectoplacental cones, and the secretion of matrix metalloproteinases. Animal experiments showed that applying this antibody before embryo implantation caused pregnancy failure in mice. Our data present direct evidence for the role of CD146 in mediating embryonic attachment and trophoblastic invasion, and provide new insight into the molecular mechanism underlying unexplained pregnancy loss and recurrent miscarriage.
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, PR China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.forename: Bairu
authors.initials: B
authors.lastname: Zhang
authors.forename: Xingang
authors.initials: X
authors.lastname: Zhao
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yixun
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiyun
authors.initials: X
authors.lastname: Yan
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D051929:CD146 Antigen / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D010064:Embryo Implantation / Q000187:drug effects; D020964:Embryo Loss / Q000378:metabolism*; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects; D014599:Uterus / Q000166:cytology / Q000187:drug effects
chemical_list: D000906:Antibodies; D051929:CD146 Antigen