Production of macrophage inflammatory protein-3α in human follicular fluid and cultured granulosa cells

Objective: To investigate the role of macrophage inflammatory protein (MIP)-3alpha in human ovulation. Design: Study of the levels of MIP-3alpha in serum and follicular fluid. The effects of interleukin (IL)-1alpha, IL-1 receptor antagonist (RA), and tumor necrosis factor (TNF)-alpha on the secretion of MIP-3alpha by primary cultured granulosa-lutein cells and an immortalized granulosa cell line (GC1a) were investigated. Setting: Research laboratory at a university medical school. Patient(s): Forty-six patients with sterility undergoing in vitro fertilization and embryo transfer (IVF-ET). Intervention(s): Follicular fluid was obtained from study participants, and granulosa-lutein cells and GCla were incubated with IL-1alpha, IL-1RA, or TNF-alpha for 4 to 32 hours. Main Outcome Measure(s): The concentration of MIP-3alpha in human follicular fluid was measured and 7 correlated with oocyte maturation. We also cultured granulosa cells and examined the regulation of MIP-3alpha production. The concentrations of MIP-3alpha in the serum, follicular fluid, and culture medium were measured using enzyme-linked immunoabsorbent assay. Result(s): Concentrations of MIP-3alpha were significantly higher in the follicular fluid, but it was not detected in the serum. Concentrations of MIP-3alpha were statistically significantly higher in the follicular fluid containing mature oocytes than in follicular fluid containing immature oocytes. The production of MIP-3alpha was markedly increased over the basal level after treatment with IL-1alpha and TNF-alpha in a dose-dependent manner. The stimulatory effect of IL-1alpha was inhibited by IL-1RA. Conclusion(s): Our data suggest that MIP-3alpha was present in follicular fluid and correlated with oocyte maturation, and was regulated by IL-1alpha and TNF-alpha. Thus, MIP-3alpha may play an important role in the human preovulatory process. (C) 2004 by American Society for Reproductive Medicine.