Novel growth factor supporting survival of murine primordial germ cells: evidence from conditioned medium of ter fetal gonadal somatic cells.

The ter (teratoma, chromosome 18) mutation causes a deficiency of primordial germ cells (PGCs) in ter/ter embryos from the ter congenic mouse strain at 8.0 days post coitum (dpc). In order to analyse the function of the ter gene, here we examined effects of conditioned medium (CM) from 14.5 dpc testicular and ovarian somatic cells of +/+, +/ter, or ter/ter genotype on mouse PGCs "mixed-cultured" with own somatic cells on feeder cells. The results showed that +/+ and +/ter CM supported survival in 9.5 and 11.5 dpc ICR PGCs but ter/ter CM did not rescue TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)-positive apoptosis in the PGCs though it did not affect 5-bromo-2-deoxyuridine incorporation in PGCs. This supportive substance in +/+ CM, not ter/ter CM, was characterized as soluble, heat labile, and larger than 30 kDa. We also found that several known growth factors for PGCs and their receptors were expressed in ter/ter testes as well as +/+ testes, suggesting the ter function is independent. Thus, it was concluded that fetal gonadal somatic cells express a novel PGC growth factor (designated as TER Factor) supporting survival of PGCs not somatic cells and that the PGC deficiency in ter/ter testes is caused by a loss of this factor.