G-CSF: A Vehicle for Communication Between Trophoblasts and Macrophages, Which May Cause Problems in Recurrent Spontaneous Abortion

Background: The etiology of about half of patients with recurrent spontaneous abortion (RSA) remains unclear. Imbalance of the immune inflammatory response at the mother-foetal interface may be one of the keys to the onset of RSA. Granulocyte-colony stimulating factor (G-CSF) is thought to have a protective effect on pregnancy and its absence may lead to pregnancy failure. However, the evidence of the described effects of G-CSF is scant. This study aimed at investigating whether the loss of G-CSF induced RSA by affecting cell communication at the maternal-foetal interface. Results: : It was found that G-CSF was mainly expressed in villus rather than decidua and expression in RSA tissues was lower than that in normal tissues. Further, the down-regulation of G-CSF in trophoblasts resulted to a decrease in cell activity. Trophoblast-derived exosomes inhibited macrophage activation, while G-CSF free exosomes did not. Intraperitoneal injection of G-CSF improved the pregnancy outcome in RSA mice and the expression of G-CSF as well as its receptor at the mother-foetal interface were also changed. Conclusion: The expression of G-CSF was found to be decreased in villi of patients with RSA. It was evident that the absence of G-CSF weakens the immune suppression of trophoblasts against macrophages and the function of trophoblasts is also impaired. Therefore, this may be a key factor in the occurrence of RSA. Further, G-CSF decreases the rate of abortion in RSA mice and may provide some assistance in the treatment of patients with RSA.