Document Detail


Reduced maternal expression of adrenomedullin disrupts fertility, placentation, and fetal growth in mice.
MedLine Citation:
PMID:  16981008     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Adrenomedullin (AM) is a multifunctional peptide vasodilator that is essential for life. Plasma AM expression dramatically increases during pregnancy, and alterations in its levels are associated with complications of pregnancy including fetal growth restriction (FGR) and preeclampsia. Using AM+/- female mice with genetically reduced AM expression, we demonstrate that fetal growth and placental development are seriously compromised by this modest decrease in expression. AM+/- female mice had reduced fertility characterized by FGR. The incidence of FGR was also influenced by the genotype of the embryo, since AM-/- embryos were more often affected than either AM+/- or AM+/+ embryos. We demonstrate that fetal trophoblast cells and the maternal uterine wall have coordinated and localized increases in AM gene expression at the time of implantation. Placentas from growth-restricted embryos showed defects in trophoblast cell invasion, similar to defects that underlie human preeclampsia and placenta accreta. Our data provide a genetic in vivo model to implicate both maternal and, to a lesser extent, embryonic levels of AM in the processes of implantation, placentation, and subsequent fetal growth. This study provides the first genetic evidence to our knowledge to suggest that a modest reduction in human AM expression during pregnancy may have an unfavorable impact on reproduction.
Authors:
Manyu Li; Della Yee; Terry R Magnuson; Oliver Smithies; Kathleen M Caron
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-09-14
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  116     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-10-03     Completed Date:  2007-01-05     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2653-62     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Adrenomedullin / genetics*,  metabolism
Animals
Decidua / metabolism
Embryo Implantation / genetics
Embryo Loss / genetics
Embryonic Development / genetics
Female
Fertility / genetics*
Fetal Death / genetics
Fetal Development / genetics*
Fetal Growth Retardation / genetics
Gene Expression / genetics
Genotype
Heterozygote
Litter Size / genetics
Mice
Mice, Knockout
Placenta / pathology
Placentation / genetics*
Pregnancy
Sex Factors
Trophoblasts / metabolism
Uterus / metabolism
Grant Support
ID/Acronym/Agency:
HD046970/HD/NICHD NIH HHS; HL49277/HL/NHLBI NIH HHS; NS031768/NS/NINDS NIH HHS; R01 HL049277/HL/NHLBI NIH HHS; R01 HL049277-14/HL/NHLBI NIH HHS; R01 HL049277-15/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
148498-78-6/Adrenomedullin
Comments/Corrections

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