title: Lentiviral Vector-Mediated Complementation Restored Fetal Viability but Not Placental Hyperplasia in Plac1-Deficient Mice.
abstract: The X-linked Plac1 gene is maternally expressed in trophoblast cells during placentation, and its disruption causes placental hyperplasia and intrauterine growth restriction. In contrast, Plac1 is also reported to be one of the upregulated genes in the hyperplastic placenta generated by nuclear transfer. However, the effect of overexpressed Plac1 on placental formation and function remained unaddressed. We complemented the Plac1 knockout placental dysfunction by lentiviral vector-mediated, placenta-specific Plac1 transgene expression. Whereas fetal development and the morphology of maternal blood sinuses in the labyrinth zone improved, placental hyperplasia remained, with an expanded the junctional zone that migrated and encroached into the labyrinth zone. Further experiments revealed that wild-type placenta with transgenically expressed Plac1 resulted in placental hyperplasia without the encroaching of the junctional zone. Our findings suggest that Plac1 is involved in trophoblast cell proliferation, differentiation, and migration. Its proper expression is required for normal placentation and fetal development.
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Osaka, Japan Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
authors.forename: Masanaga
authors.initials: M
authors.lastname: Muto
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fujihara
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Tobita
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Daiji
authors.initials: D
authors.lastname: Kiyozumi
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Osaka, Japan Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan ikawa@biken.osaka-u.ac.jp.
authors.forename: Masahito
authors.initials: M
authors.lastname: Ikawa
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000378:metabolism; D049109:Cell Proliferation; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics / Q000473:pathology; D005328:Fetal Viability / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D005816:Genetic Complementation Test; D005822:Genetic Vectors; D006965:Hyperplasia; D016086:Lentivirus / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D053652:Nuclear Transfer Techniques; D010920:Placenta / Q000473:pathology*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000172:deficiency* / Q000235:genetics*; D019076:Transgenes / Q000235:genetics; D014327:Trophoblasts
chemical_list: C587952:PLAC1 protein, mouse; D011257:Pregnancy Proteins
keywords: imprinting; intrauterine growth restriction; knockout; lentiviral vector; nuclear transfer