Document Detail

Differential roles of renin and angiotensinogen in the feto-maternal interface in the development of complications of pregnancy.
MedLine Citation:
PMID:  15695374     Owner:  NLM     Status:  MEDLINE    
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.
Eriko Takimoto-Ohnishi; Tomoko Saito; Junji Ishida; Junji Ohnishi; Fumihiro Sugiyama; Ken-Ichi Yagami; Akiyoshi Fukamizu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-02-03
Journal Detail:
Title:  Molecular endocrinology (Baltimore, Md.)     Volume:  19     ISSN:  0888-8809     ISO Abbreviation:  Mol. Endocrinol.     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-04-26     Completed Date:  2005-08-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8801431     Medline TA:  Mol Endocrinol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1361-72     Citation Subset:  IM    
Center for Tsukuba Advanced Research Alliance, Institute of Applied Biochemistry, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan.
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MeSH Terms
Angiotensinogen / genetics,  metabolism*
Gene Expression / physiology
Mice, Transgenic
Placenta / metabolism*
Pregnancy / metabolism*
RNA, Messenger / metabolism
Renin / genetics,  metabolism*
Renin-Angiotensin System / physiology
Reg. No./Substance:
0/RNA, Messenger; 11002-13-4/Angiotensinogen; EC

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