Kisspeptin-10, a KiSS-1/metastin-derived decapeptide, is a physiological invasion inhibitor of primary human trophoblasts

J Cell Sci. 2004 Mar 15;117(Pt 8):1319-28. doi: 10.1242/jcs.00971.

Abstract

Trophoblast invasion of the uterine extracellular matrix, a critical process of human implantation and essential for fetal development, is a striking example of controlled invasiveness. To identify molecules that regulate trophoblast invasion, mRNA signatures of trophoblast cells isolated from first trimester (high invasiveness) and term placentae (no/low invasiveness) were compared using U95A GeneChip microarrays yielding 220 invasion/migration-related genes. In this 'invasion cluster', KiSS-1 and its G-protein-coupled receptor KiSS-1R were expressed at higher levels in first trimester trophoblasts than at term of gestation. Receptor and ligand mRNA and protein were localized to the trophoblast compartment. In contrast to KiSS-1, which is only expressed in the villous trophoblast, KiSS-1R was also found in the extravillous trophoblast, suggesting endocrine/paracrine activation mechanisms. The primary translation product of KiSS-1 is a 145 amino acid polypeptide (Kp-145), but shorter kisspeptins (Kp) with 10, 13, 14 or 54 amino acid residues may be produced. We identified Kp-10, a dekapeptide derived from the primary translation product, in conditioned medium of first trimester human trophoblast. Kp-10, but not other kisspeptins, increased intracellular Ca(2+) levels in isolated first trimester trophoblasts. Kp-10 inhibited trophoblast migration in an explant as well as transwell assay without affecting proliferation. Suppressed motility was paralleled with suppressed gelatinolytic activity of isolated trophoblasts. These results identified Kp-10 as a novel paracrine/endocrine regulator in fine-tuning trophoblast invasion generated by the trophoblast itself.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Calcium / metabolism
  • Cell Movement / drug effects*
  • Culture Media, Conditioned / chemistry
  • Culture Media, Serum-Free
  • Female
  • Gene Expression
  • Gene Expression Profiling
  • Humans
  • Immunohistochemistry
  • Kisspeptins
  • Oligonucleotide Array Sequence Analysis
  • Oligopeptides
  • Organ Culture Techniques
  • Peptides / chemistry
  • Peptides / metabolism
  • Peptides / pharmacology
  • Peptides / physiology*
  • Placenta / chemistry
  • Pregnancy
  • Pregnancy Trimester, First
  • Proteins / chemistry*
  • RNA, Messenger / metabolism
  • Trophoblasts / chemistry
  • Trophoblasts / cytology*
  • Trophoblasts / physiology*
  • Tumor Suppressor Proteins

Substances

  • Culture Media, Conditioned
  • Culture Media, Serum-Free
  • KISS1 protein, human
  • Kisspeptins
  • Oligopeptides
  • Peptides
  • Proteins
  • RNA, Messenger
  • Tumor Suppressor Proteins
  • Calcium