title: Ggnbp2 Is Essential for Pregnancy Success via Regulation of Mouse Trophoblast Stem Cell Proliferation and Differentiation.
abstract: The Ggnbp2 null mutant embryos died in utero between Embryonic Days 13.5 to 15.5 with dysmorphic placentae, characterized by excessive nonvascular cell nests consisting of proliferative trophoblastic tissue and abundant trophoblast stem cells (TSCs) in the labyrinth. Lethality of Ggnbp2 null embryos was caused by insufficient placental perfusion as a result of remarkable decreases in both fetal and maternal blood vessels in the labyrinth. These defects were accompanied by a significant elevation of c-Met expression and phosphorylation and its downstream effector Stat3 activation. Knockdown of Ggnbp2 in wild-type TSCs in vitro provoked the proliferation but delayed the differentiation with an upregulation of c-Met expression and an enhanced phosphorylation of c-Met and Stat3. In contrast, overexpression of Ggnbp2 in wild-type TSCs exhibited completely opposite effects compared to knockdown TSCs. These results suggest that loss of GGNBP2 in the placenta aberrantly overactivates c-Met-Stat3 signaling, alters TSC proliferation and differentiation, and ultimately compromises the structure of placental vascular labyrinth. Our studies for the first time demonstrate that GGNBP2 is an essential factor for pregnancy success acting through the maintenance of a balance of TSC proliferation and differentiation during placental development.
authors.affiliation: Department of OB/GYN & Women's Health, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Shengqiang
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of OB/GYN & Women's Health, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Moore
authors.affiliation: Department of OB/GYN & Women's Health, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of OB/GYN & Women's Health, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Xian
authors.initials: X
authors.lastname: Li
authors.affiliation: Birth Defects Center, Department of Molecular, Cellular and Craniofacial Biology, University of Louisville School of Dentistry, Louisville, Kentucky.
authors.forename: Huaxin
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of OB/GYN & Women's Health, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of OB/GYN & Women's Health, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Yan
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of OB/GYN & Women's Health, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Fengying
authors.initials: F
authors.lastname: Xing
authors.affiliation: Department of OB/GYN & Women's Health, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Yangbin
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of OB/GYN & Women's Health, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Henry C
authors.initials: HC
authors.lastname: Bohler
authors.affiliation: Birth Defects Center, Department of Molecular, Cellular and Craniofacial Biology, University of Louisville School of Dentistry, Louisville, Kentucky.
authors.forename: Jixiang
authors.initials: J
authors.lastname: Ding
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas.
authors.forename: Austin J
authors.initials: AJ
authors.lastname: Cooney
authors.affiliation: Division of Life Sciences and Center for Nutrigenomics & Applied Animal Nutrition, Alltech Inc., Nicholasville, Kentucky zlan@alltech.com.
authors.forename: Zijian
authors.initials: Z
authors.lastname: Lan
authors.affiliation: Department of OB/GYN & Women's Health, University of Louisville School of Medicine, Louisville, Kentucky zhenmin.lei@louisville.edu.
authors.forename: Zhenmin
authors.initials: Z
authors.lastname: Lei
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D005260:Female; D051379:Mice; D008822:Mice, Transgenic; D010766:Phosphorylation; D010929:Placentation / Q000235:genetics*; D011247:Pregnancy; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C497527:GGNBP2 protein, mouse; D050796:STAT3 Transcription Factor; D019859:Proto-Oncogene Proteins c-met
keywords: Ggnbp2; Stat3; c-Met; knockout; labyrinth; placenta; trophoblast stem cells