Mesenchymally-derived insulin-like growth factor 1 provides a paracrine stimulus for trophoblast migration.
BACKGROUND
Trophoblast migration into maternal decidua is essential for normal pregnancy. It occurs in a defined time window, is spatially highly restricted, and is aberrant in some pathological pregnancies, but the control mechanisms are as yet ill-defined. At the periphery of the placenta, chorionic villi make contact with decidua to form specialised anchoring sites that feed interstitially migrating cytotrophoblast into the placental bed.


RESULTS
Explants of first trimester mesenchymal villi on collagen type I developed cytotrophoblast outgrowths from the villous tips. However, in medium changed daily, cells did not progress to a migratory phenotype, remaining instead as a contiguous multi-layered sheet. This suggested the need for another migration stimulus. To test the possibility that this might arise from mesenchymal cells, serum-free conditioned medium from first trimester placental fibroblasts was added to explant cultures. Cytotrophoblasts were stimulated to migrate in streams across the gel. Affinity depletion of Insulin-like growth factor from fibroblast medium reduced streaming activity, while the addition of exogenous IGF-I (10 ng/ml) to serum-free medium produced a streaming phenotype. IGF receptor type 1 (IGFR1) was present on cells in the columns, and streaming could be inhibited by antibody to this receptor. IGF-II and activin, known stimulators of cytotrophoblast migration, were also active in this model.


CONCLUSIONS
These data suggest a paracrine interaction between villous mesenchyme and the cytotrophoblast in anchoring sites that stimulates trophoblast infiltration of decidua. Such a signal would be self-limiting since it diminishes with distance from the placenta. This is a novel mechanism in placental development.
Lacey
Helen
H
Schools of Medicine and Biological Sciences University of Manchester, Manchester, UK. Helen.Lacey@man.ac.uk
Haigh
Teresa
T
Westwood
Melissa
M
Aplin
John D
JD
D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry; D003595:Cytoplasmic Streaming / Q000502:physiology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology*; D008648:Mesoderm / Q000737:chemistry* / Q000378:metabolism; D019899:Paracrine Communication / Q000502:physiology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000502:physiology; D017526:Receptor, IGF Type 1 / Q000502:physiology; D014327:Trophoblasts / Q000166:cytology*
D003470:Culture Media; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; C065700:myotrophin; D017526:Receptor, IGF Type 1