Colony-stimulating factor-1 (CSF-1) expression in the uteroplacental unit of mice with spontaneous and induced pregnancy loss

CSF-1 plays an important role in female reproduction and normal embryo deve lopment. To understand further CSF-1 function in normal and, especially, in compromised pregnancy, we studied the pattern of its mRNA expression as we ll as expression of its receptor (c-fms) in the uteroplacental units of mic e with induced (cyclophosphamide (CY)-treated) and spontaneous (CBA/JxDBA/2 J mating combination) pregnancy loss. RNase protection analysis demonstrate d the presence of two forms of CSF-1 mRNA in the uteroplacental unit corres ponding to 1400- and 263-bp protective fragments. Densitometric analysis de monstrated that the level of 1400-bp mRNA form was decreased by 40% in the uteroplacental units of mice with CY-induced pregnancy-loss compared with t he control mice-about 20% decrease in 263-bp protective fragment was regist ered in resorbing versus non-resorbed placenta of CBA/J females mated to DB A/2J males. As judged by in situ hybridization assay, CSF-1 mRNA transcript s were localized in the uterine epithelium and stroma, while c-fms mRNA was found mainly in the trophoblast. The number of metrial gland cells as well as the number of uterine leucocytes expressing CSF-1 and c-fms mRNAs was s ubstantially lower in the uteroplacental unit of mice with pregnancy loss t han in control animals. Maternal immunostimulation, while significantly dec reasing the resorption rate in mice with CY-induced pregnancy loss, also st rengthened CSF-1 mRNA expression at the fetomaternal interface and resulted in reconstitution in the number of CSF-1(+) uterine leucocytes and metrial gland cells. These data suggest a role for uterine CSF-1 in the physiology of normal and compromised pregnancy and demonstrate a possible involvement of CSF1-associated signalling in mechanisms of placenta and endometrium re pair following immunopotentiation.