Granulocyte Colony-Stimulating Factor (G-CSF) in the Mechanism of Human Ovulation and its Clinical Usefulness

Abstract

In 1980, Espey proposed a famous hypothesis that mammalian ovulation is comparable to an inflammatory reaction and many researches have proved the validity of his hypothesis in the last three decades. For example, interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)- alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF) and other inflammatory cytokines presence was proven in the preovulatory follicle. Since granulocyte is the major leukocyte and it plays a very important role during inflammation, the importance of granulocyte and its related cytokine, granulocyte colony-stimulating factor (G-CSF) in the mechanism of human ovulation is easily predictable. G-CSF is one of the hemopoietic cytokines and it has strong positive effects on granulocytes. G-CSF increases the number of granulocytes and it improves the function of granulocytes. In this review, the participation of leukocytes in the ovulation mechanism is demonstrated first. Second, the participation of G-CSF is shown in comparison with the above mentioned cytokines. Finally, since G-CSF has been used for more than 20 years as a medicine without severe side effects in the field of oncology, the clinical application of G-CSF for the treatment of an ovulation disorder, luteinized unruptured follicle (LUF), will be discussed.

Upregulation of MMPs in placentas of patients with gestational diabetes mellitus: Involvement of the PI3K/Akt pathway

“…These alternatively spliced forms of CSF3R may exhibit different functions and regulatory mechanisms. Accumulating evidence has shown that CSF3 plays an essential role in placental metabolism, trophoblast development, decidualization of endometrial stromal cells, and ovulation by binding to CSF3R to regulate multiple signaling pathways [ [52] , [53] , [54] , [55] ]. CSF3 could promote trophoblast invasion and migration through activating the PI3K/Akt signaling pathway, thereby involving the normal pregnancy program [ 56 ].…”

Immunology and Immunotherapy of Endometriosis

“…Where no G-CSF was administered, ovulation was abnormal with functional cyst (LUF) formation. Up to 90% of patients with infertility ovulated after the administration of the stimulating factor, compared to only 50% of the controls [64]. Therefore, G-CSF appears to be a safe and effective treatment for LUF syndrome associated with endometriosis.…”

Pathogenetic factors involved in recurrent pregnancy loss from multiple aspects

“…CSFs are involved in numerous reproductive functions, including ovulation, embryo implantation, placental growth, and embryo development [67]. During ovulation, CSF-3/G-CSF promotes ovulation through leukocyte attraction and activation [68]. After ovarian hyper-stimulation for in vitro fertilization, the cumulus oophorus cells synthesize and secrete CSF-1/M-CSF, and this synthesis is highly dependent on progesterone.…”