Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Lung inflammatory injury and tissue repair (Jul 2023)
    • Immune Environment in Glioblastoma (Feb 2023)
    • Korsmeyer Award 25th Anniversary Collection (Jan 2023)
    • Aging (Jul 2022)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Research letters
    • Letters to the editor
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Research letters
  • Letters to the editor
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Reduced maternal expression of adrenomedullin disrupts fertility, placentation, and fetal growth in mice
Manyu Li, … , Oliver Smithies, Kathleen M. Caron
Manyu Li, … , Oliver Smithies, Kathleen M. Caron
Published October 2, 2006
Citation Information: J Clin Invest. 2006;116(10):2653-2662. https://doi.org/10.1172/JCI28462.
View: Text | PDF
Research Article Reproductive biology

Reduced maternal expression of adrenomedullin disrupts fertility, placentation, and fetal growth in mice

  • Text
  • PDF
Abstract

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

×

Figure 7

Maternal uterine expression of AM is localized to implantation sites.

Options: View larger image (or click on image) Download as PowerPoint
Maternal uterine expression of AM is localized to implantation sites.
  ...
(A–E) In situ hybridizations for AM gene expression in consecutive serial sections of an implantation site isolated from a wild-type cross at E5. The schematic diagram depicts the approximate location of the series of sections shown in A–E, which were each approximately 150 μm apart. Note the gradual increase in maternal uterine AM gene expression that peaked at the center of the implantation site in C next to the developing embryo. (F) High-power magnification of the implantation site shown in C. Note the presence of the embryo (e) and yolk sac cavity (ys). The fetal tissue is surrounded by a thin line of intense, punctuate staining, likely representative of mural TGCs. Maternal expression of AM can be visualized in the luminal epithelium (le) and surrounding stroma (s). H&E staining of wild-type placentas at E9.5 (G) and E14.5 (I), with corresponding in situ hybridizations of serial sections (H and J, respectively) showing robust AM expression in the maternal decidua (MD) compared with weak expression in the fetal placenta (FP). m, mesometrium.

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts