Mechanisms of Action of G-CSF Treatment in Recurrent Pregnancy Loss: Immunological and Trophoblast Growth Pathways

Background: We used successfully G-CSF in the treatment of Recurrent Pregnancy Loss (RPL), but there are no data on its mechanisms of action onpregnancy.

Objective: In order to assess the effects of G-CSF on maternal immune-system and decidual immune-cells, as well as on trophoblast expression of several markers of cellular growth we condocted this study on women with RPL treated with G-CSF or placebo.

Methods: Blood samples of 15 RPL women treated with G-CSF, of 15 RPL women treated with placebo and of 15 women with physiological pregnancy were collected at 8^th week of gestation and used to assess Treg cell (Foxp-3+) levels in maternal circulation. Furthermore, specimens of deciduas and trophoblast of 10 abortive first trimester pregnancies obtained from 10 RPL women treated with G-CSF that re-aborted for fetal chromosomal abnormalities. As controls 10 specimens of first trimester pregnancies obtained from 10 RPL women treated with placebo that re-aborted and 10 specimens obtained from first trimester pregnancy underwent voluntary termination. All these specimens were used to conduct an immunohistochemical study to assess the expression of Foxp3, c-kit, VEGF and VEGFR-2; a semiquantitative analysis was performed.

Results: Treg levels in peripheral blood of RPL women treated with G-CSF during pregnancy were significantly higher than controls (P<0.001). Also in the decidual specimens of women treated with G-CSF the number of cells expressing Foxp3 was significantly higher than in controls (P<0.001). Also for c-kit VEGF and VEGFR-2, -specimens obtained from RPL women treated with G-CSF showed significantly higher levels (P<0.001).

Conclusion: Our data showed that G-CSF treatment has an effect on maternal local and general immune system, as well as on trophoblast growth.