Serum-dependent effects of IGF-I and insulin on proliferation and invasion of human first trimester trophoblast cell models

Histochem Cell Biol. 2002 May;117(5):391-9. doi: 10.1007/s00418-002-0403-5. Epub 2002 Apr 16.


Extravillous cytotrophoblasts are specialised epithelial cells of the placenta that proliferate or invade the maternal decidua. Little is known about the mechanisms that regulate these processes. Here the effects of several insulin and insulin-like growth factor-I (IGF-I) doses, either singly or in synergy with serum, on human chorionic gonadotropin-beta (hCG-beta) secretion (RIA), proliferation (cell counting, cyclin B(1) levels) and invasion [Matrigel invasion assay, secretion of matrix metalloproteinases (MMP) 2 and 9] were investigated. The choriocarcinoma cell lines BeWo, JAR and JEG-3 served as models for first trimester human trophoblasts. Both growth factors altered hCG-beta secretion and proliferation dependent on the cell line. Insulin stimulated proliferation in JAR cells and, to a lesser extent, in JEG-3 cells, and when cultured in serum-free medium, BeWo was not affected. Invasion was not affected although proMMP-2 levels in culture medium were altered under some conditions. A strong synergistic effect with serum was noted. In the presence of serum both growth factors reduced proliferation and invasion in a similar fashion. Since the cell models differ by their degree of differentiation, the data demonstrate that the effects of insulin and IGF-I strongly depend on serum and the degree of differentiation. It can be speculated that IGF-I can take on tasks of insulin in the regulation of trophoblast functions under conditions of insulinopenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Cell Count
  • Cell Division / drug effects*
  • Cell Movement / drug effects
  • Chorionic Gonadotropin, beta Subunit, Human / drug effects
  • Chorionic Gonadotropin, beta Subunit, Human / metabolism
  • Culture Media / chemistry
  • Culture Media / pharmacology
  • Cyclin B / drug effects
  • Cyclin B / metabolism
  • Cyclin B1
  • Dose-Response Relationship, Drug
  • Enzyme Precursors / drug effects
  • Enzyme Precursors / metabolism
  • Female
  • Fetal Blood / physiology*
  • Humans
  • Insulin / pharmacology*
  • Insulin-Like Growth Factor I / pharmacology*
  • Matrix Metalloproteinase 1 / drug effects
  • Matrix Metalloproteinase 1 / metabolism
  • Matrix Metalloproteinase 2 / drug effects
  • Matrix Metalloproteinase 2 / metabolism
  • Pregnancy
  • Pregnancy Trimester, First
  • Trophoblasts / cytology
  • Trophoblasts / drug effects
  • Trophoblasts / metabolism
  • Tumor Cells, Cultured / cytology
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / metabolism


  • CCNB1 protein, human
  • Chorionic Gonadotropin, beta Subunit, Human
  • Culture Media
  • Cyclin B
  • Cyclin B1
  • Enzyme Precursors
  • Insulin
  • Insulin-Like Growth Factor I
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 1