G-CSF: A vehicle for communication between trophoblasts and macrophages which may cause problems in recurrent spontaneous abortion. (April 2022)

• Record Type: Journal Article
• Authors: Gao, Peng; Zha, Ying; Wei, Lijie; Zhou, Xuan; Zhu, Shenglan; Zhang, Huiting; Gao, Xuan; Jiang, Yi; Chen, Yuting; Li, Jiaqi; Zhang, Jingyi; Yu, Jun; Wang, Shaoshuai; Liu, Haiyi; Feng, Ling
• Is Part Of: Placenta. Volume 121(2022)
• Page Start: 164
• Page End: 172
• Publication Date: 2022-04
• Subjects: Recurrent spontaneous abortion -- Trophoblast -- Macrophage -- G-CSF -- Exosome; Placenta -- Periodicals; Reproduction -- Periodicals; Placenta -- Periodicals; Placenta -- Périodiques; Reproduction -- Périodiques; 612.63
• DOI: 10.1016/j.placenta.2022.03.125
• Languages: English
• ISSNs: 0143-4004

Abstract

Abstract: Introduction: The etiology of approximately half of patients with recurrent spontaneous abortion (RSA) has yet to be established. Granulocyte-colony stimulating factor (G-CSF) exerts a protective effect on pregnancy and its absence may lead to pregnancy failure. However, the effects and mechanisms of G-CSF activities have not been fully explored. Therefore, we aimed at evaluating whether a loss of G-CSF induces RSA by affecting cell communication at the maternal-foetal interface. Methods: Villous and decidual tissues were obtained from participants and expression levels of G-CSF determined by qRT-PCR, Western blot and immunohistochemistry. G-CSF levels in trophoblasts were downregulated by siRNA. Exosomes were extracted from trophoblasts and co-cultured with macrophages. Molecular expression levels of key genes were determined by qRT-PCR and Western blot. Migration and proliferation of cells were evaluated by transwell and CCK8 assays. The RSA mice models were intraperitoneally administered with G-CSF to assess pregnancy outcomes and expression profiles of G-CSF as well as its receptor at the mother-foetal interface. Results: Relative to the decidua, G-CSF was highly expressed in the villus, and expression levels were low in RSA tissues compared to normal tissues. Down-regulation of G-CSF in the trophoblast cell line (HTR-8/SVneo) by siRNA was associated with a decrease in cell activities. Trophoblast-derived exosomes inhibited the activation of the macrophage cell line (RAW264.7), whereas G-CSF free exosomes had no effects on macrophage activation. Intraperitoneal administration of G-CSF improved pregnancy outcomes in RSA mice and increased the amounts of G-CSF at the maternal-foetal interface. Discussion: G-CSF levels were downregulated in villi of RSA patients. The absence of G-CSF impaired the proliferation as well as migration capacities of trophoblasts, and weakened the suppression of trophoblasts against macrophages. This implies that suppressed G-CSF levels may be a key factor in RSA occurrence. G-CSF decreased the rate of abortion in RSA mice, thus, it could be a treatment option for RSA patients. Highlights: G-CSF is decreased in patients with RSA comparing with normal pregnant women. G-CSF regulates trophoblast - macrophage communication through exosomes. G-CSF decreases the rate of abortion in RSA mice.