title: Tissue-wide overexpression of alpha-T-catenin results in aberrant trophoblast invasion but does not cause embryonic mortality in mice.
abstract: Transcriptional activation of CTNNA3, encoding αT-catenin, by the Y153H mutated form of the human STOX1 transcription factor was proposed to be responsible for altered fetal trophoblast invasion into the maternal endometrium during placentation in pre-eclampsia. Here we have generated a mouse model to investigate the in vivo effects of ectopic αT-catenin expression on trophoblast invasion. Histological analysis was used to determine the invasive capacities of trophoblasts from transgenic embryos, as well as proliferation rates of spongiotrophoblasts in the junctional zone. Augmented expression of αT-catenin reduced the number of invading trophoblasts but did not cause embryonic mortality. The, αT-catenin positive cells could still invade into the decidual layer and migrated as deeply as wild-type trophoblasts. Furthermore, the junctional zone is enlarged in placentas of mice overexpressing αT-catenin due to hyperproliferation of the residing spongiotrophoblasts, suggesting a pivotal role of αT-catenin levels in the control of the proliferative versus invasive state of trophoblasts during placentation. Our study provides, for the first time, in vivo data on the effects of increased levels of αT-catenin in the placenta.
authors.affiliation: Department for Molecular Biomedical Research, VIB, Technologiepark 927, B-9052 Ghent, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Tyberghein
authors.forename: S
authors.initials: S
authors.lastname: Goossens
authors.forename: J J
authors.initials: JJ
authors.lastname: Haigh
authors.forename: F
authors.initials: F
authors.lastname: van Roy
authors.forename: J
authors.initials: J
authors.lastname: van Hengel
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006579:Heterozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D010920:Placenta / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D010929:Placentation / Q000502:physiology*; D011247:Pregnancy; D011506:Proteins / Q000235:genetics; D022661:RNA, Untranslated; D014327:Trophoblasts / Q000166:cytology / Q000502:physiology*; D051178:alpha Catenin / Q000032:analysis / Q000235:genetics* / Q000502:physiology
chemical_list: C575065:CTNNA3 protein, mouse; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; D011506:Proteins; D022661:RNA, Untranslated; D051178:alpha Catenin