Mast cells rescue implantation defects caused by c-kit deficiency

Cell Death Dis. 2013 Jan 17;4(1):e462. doi: 10.1038/cddis.2012.214.


Various physiologically relevant processes are regulated by the interaction of the receptor tyrosine kinase (c-Kit) and its ligand stem cell factor (SCF), with SCF known to be the most important growth factor for mast cells (MCs). In spite of their traditional role in allergic disorders and innate immunity, MCs have lately emerged as versatile modulators of a variety of physiologic and pathologic processes. Here we show that MCs are critical for pregnancy success. Uterine MCs presented a unique phenotype, accumulated during receptivity and expanded upon pregnancy establishment. Kit(W-sh/W-sh) mice, whose MC deficiency is based on restricted c-Kit gene expression, exhibited severely impaired implantation, which could be completely rescued by systemic or local transfer of wild-type bone marrow-derived MCs. Transferred wild-type MCs favored normal implantation, induced optimal spiral artery remodeling and promoted the expression of MC proteases, transforming growth factor-β and connective tissue growth factor. MCs contributed to trophoblast survival, placentation and fetal growth through secretion of the glycan-binding protein galectin-1. Our data unveil unrecognized roles for MCs at the fetomaternal interface with critical implications in reproductive medicine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Connective Tissue Growth Factor / metabolism
  • Female
  • Galectin 1 / deficiency
  • Galectin 1 / genetics
  • Galectin 1 / metabolism
  • Mast Cells / metabolism*
  • Mast Cells / transplantation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pregnancy
  • Proto-Oncogene Proteins c-kit / deficiency
  • Proto-Oncogene Proteins c-kit / genetics
  • Proto-Oncogene Proteins c-kit / metabolism*
  • Stem Cell Factor / metabolism
  • Transforming Growth Factor beta / metabolism
  • Uterus / anatomy & histology


  • Galectin 1
  • Stem Cell Factor
  • Transforming Growth Factor beta
  • Connective Tissue Growth Factor
  • Proto-Oncogene Proteins c-kit