Effects of Decidual Cell Supernatants and Lymphokines on Murine Trophoblast Growth in Vitro1

Blastocysts were flushed from CD1 mice and were cultured in plastic or laminin-coated plates as an in vitro model of implantation. The purified cytokines epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) markedly stimulated 3H-thymidine incorporation; but recombinant murine granulocyte-macrophage colony-stimulating factor (GM-CSF), which might be produced by alloantigen-stimulated T cells at the feto-maternal interface, had no growth-stimulating effect. Indeed, higher nonphysiological concentrations of GM-CSF manifested a toxic inhibition. Surprisingly, a purified nonrecombinant murine GM-CSF preparation induced proliferation of both blastocyst and ectoplacental cone trophoblast whereas recombinant murine (and human) GM-CSF had no effect, indicating that the growth stimulation may have been due to a contaminant. Decidual supernatants prepared on Days 5.5-6.5 of pregnancy from mice with high abortion rates (DBA/2-mated CBA/J) had no toxic or stimulating effect on blastocyst trophoblast outgrowth compared to similarly prepared supernatants from low-abortion-rate DBA/2-mated C3H/HeJ mice. These data suggest that it is not GM-CSF that is crucial for the trophoblast proliferation that determines the success of pregnancy.