Macrophage colony stimulating factor(M-CSF) and its receptor(M-CSFR) expression in the human luteinized granulose cells(GCS) is poitively correlated with IVF-ET pregnancy outcome

There have been studied about the effect of macrophage colony stimulating factor (M-CSF) and its receptor (M-CSFR) on folliculogenesis and ovulation. In our previous study, we detected the expression of M-CSF and M-CSFR by human ovary and luteinized granulosa cells (GCs). The purpose of this study is to understand the functional role of M-CSF and it’s receptor in luteinized GCs and their results are compared with IVF-ET pregnancy outcome. Cross-sectional study We investigated expression levels of M-CSF and M-CSFR genes in luteinized GCs from 166 IVF patients. These genes were divided into four groups according to their expression patterns (M-CSF P/M-CSFR P vs. M-CSF P/M-CSFR N vs. M-CSF N/M-CSFR P vs. M-CSF N/M-CSFR N) and their results were compared with clinical outcome. To confirm the autocrine and paracrine control mechanisms of the M-CSF and M-CSFR during folliculogenesis, GC was cultured for one week in culture medium supplemented with rhM-CSF. Cell proliferation was assessed by MTT assay and the expression of M-CSFR and NPR2 mRNA were analyzed by RT-PCR. The M-CSF and M-CSFR were detected in GCs of human ovarian follicle through immunohistochemistry, and their mRNAs were highly expressed in GCs derived from pregnant patients compared to those from non-pregnant women. The pregnancy rate according to gene expression was significantly higher in M-CSF P/M-CSFR P group (M-CSF P/M-CSFR P vs. M-CSF P/M-CSFR N vs. M-CSF N/M-CSFR P vs. M-CSF N/M-CSFR N: 85.7% vs. 25.0% vs. 40.5% vs. 0.0%). These groups were comparable with respect to patients' characteristics such as age of patients, infertility duration. The growth rate of GC cells grown in the medium supplemented with rhM-CSF was increased (126±40.02 vs. 145.75±50.87) and M-CSFR gene expression was increased, while NPR2 gene expression was decreased. In this study, we confirmed that the expression of M-CSF and M-CSFR has positively correlation with IVF-ET pregnancy outcome. In rhM-CSF-treated group, GC proliferation rate and M-CSFR expression were increased and NPR2 expression was decreased. These result indicate that M-CSF influences folliculogenesis through direct action on GCs, also may regulate follicular development by controlling autocrine and paracrine mechanisms. Our study suggests that M-CSF is involved in folliculogenesis and partly promotes ovulation by influencing ovarian macrophages.