Adrenomedullin 2/Intermedin Regulates HLA-G in human trophoblasts

Madhu Chauhan, Meena Balakrishnan, Uma Yallampalli, Janice Endsley, Gary Hankins, Regan Theiler, Chandra Yallampalli

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Adrenomedullin 2 (ADM2), also referred to as intermedin (IMD), is expressed in trophoblast cells in human placenta and enhances the invasion and migration of first-trimester HTR-8SV/ neo cells. Further infusion of ADM2 antagonist in pregnant rat causes fetoplacental growth restriction, suggesting a role for ADM2 in maintaining a successful pregnancy. This study was undertaken to assess whether ADM2 protein is present in decidual tissue and colocalized with HLA-G-positive cytotrophoblast cells and natural killer cells; to assess whether ADM2 regulates expression of HLA-G in trophoblast cells; and to identify whether mitogen-activated protein kinase (MAPK) signaling pathway is involved in ADM2-induced trophoblast cell invasion and migration. Using immunohistochemical methods and RT-PCR, this study shows that ADM2 protein is colocalized with HLA-G-expressing cytotrophoblast cells as well as with NCAM1 (CD56) immunoreactivity in human first-trimester decidual tissue, and that ADM2 mRNA is expressed in peripheral blood natural killer cells. Further, ADM2 dose dependently increases the expression of HLA-G antigen in HTR-8SV/neo cells as well as in term placental villi explants, suggesting involvement of ADM2 in the regulation of HLA-G in trophoblast cells. In addition, interference with the activity of RAF and MAPK3/1 by their inhibitors, manumycin and U0126, respectively, reduces ADM2-induced HTR-8SV/neo cell invasion and migration. In summary, this study suggests a potential involvement for ADM2 in regulating HLA-G antigen at the maternal-fetal interface in human pregnancy and facilitating trophoblast invasion and migration via MAPK3/1 phosphorylation.

Original languageEnglish (US)
Pages (from-to)1232-1239
Number of pages8
JournalBiology of reproduction
Issue number6
StatePublished - Dec 1 2011


  • Early development
  • Early placental development
  • HLA-G
  • MAPK3/1 signaling
  • Placenta
  • Placentation
  • Pregnancy
  • Trophoblast

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology


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