Macrophage secretory products and sperm zona pellucida binding

OBJECTIVE: To determine if exposure of human gametes to macrophage secretor y products reduces sperm binding to the zona pellucida, and to determine wh ich cytokine(s) may be responsible for this effect. METHODS: A human macrophage cell line was cultured and either activated wit h lipopolysaccharide for 2 hours and then washed or left unactivated. Cultu re-conditioned media from activated or unactivated cells was used in hemizo na assay. Hemizonae were incubated with sperm suspended in culture medium f rom either unactivated macrophages or activated macrophages, with the match ing hemizona incubated with sperm suspended in control medium. Matching hem izonae were incubated with sperm suspended in unactivated macrophage medium paired with sperm suspended in activated macrophage culture medium. Condit ioned medium from activated macrophages was found to have elevated levels o f tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta, and transfor ming growth factor-beta, therefore, gametes were also exposed to these cyto kines followed by the hemizona assay. After each incubation, the number of sperm tightly bound to the outer surface of each hemizona was determined. RESULTS: Exposure of gametes to activated and unactivated macrophage cultur e-conditioned media significantly decreases sperm binding to the zona pellu cida, with medium from activated macrophages inducing the greatest effect ( P < .05). Exposure of sperm to TNF-alpha significantly impaired sperm bindi ng (P < .05), whereas other cytokines tested had no effect. CONCLUSION: These results suggest that macrophage secretory products in the basal and activated state may be a factor in endometriosis-associated infe rtility through the interference of sperm binding to the zona pellucida, an d that TNF-alpha is a key cytokine responsible for this effect. (C) 2001 by the American College of Obstetricians and Gynecologists.)