title: Differential roles of renin and angiotensinogen in the feto-maternal interface in the development of complications of pregnancy.
abstract: We previously identified a transgenic mouse model that developed pregnancy-associated hypertension (PAH) and intrauterine growth restriction (IUGR) by mating females expressing human angiotensinogen (hANG) with males expressing human renin (hRN). These phenotypic defects were not observed in the opposite type of mating combination, despite the feto-placental overexpression of hRN and hANG detected in both types of crossbreeding. Detailed analysis of transgene localization in the labyrinth and its permeability to the maternal circulation revealed that hRN produced in trophoblast giant cells was secreted into the maternal circulation, whereas hANG, produced in chorionic trophoblasts and trophoblastic epithelium, was undetectable in the maternal plasma, probably due to their distinct spatial and temporal expression in labyrinth. These results demonstrated that PAH and IUGR could be mediated by feto-placental hRN through its permeability to the maternal circulation, not by feto-placental hANG production. Furthermore, overexpression of maternally derived hANG in decidua and spiral arteries of pregnant females with PAH and IUGR raises the possibility of local activation of the renin-angiotensin system and its pathophysiological effects on placental hypoperfusion in complications of pregnancy. This study provides in vivo evidence that the cell-specific expression of RN and ANG in the feto-maternal interface impacts their differential roles in pregnancy.
authors.affiliation: Center for Tsukuba Advanced Research Alliance, Institute of Applied Biochemistry, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Takimoto-Ohnishi
authors.forename: Tomoko
authors.initials: T
authors.lastname: Saito
authors.forename: Junji
authors.initials: J
authors.lastname: Ishida
authors.forename: Junji
authors.initials: J
authors.lastname: Ohnishi
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Sugiyama
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Yagami
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Fukamizu
mesh_terms: D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D005260:Female; D015870:Gene Expression / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012083:Renin / Q000235:genetics / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000502:physiology
chemical_list: D012333:RNA, Messenger; D000808:Angiotensinogen; D012083:Renin