Direct effect of macrophage migration inhibitory factor on sperm function: possible involvement in endometriosis-associated infertility

Objective: To evaluate the effect of macrophage migration inhibitory, factor (NU) on sperm capacitation, a maturational process that occurs in the female reproductive tract and enables spermatozoa to become fully competent at fertilizing the oocyte. Design: Incubation of Percoll-washed spermatozoa with varying concentrations of human recombinant MIF or fetal cord serum (positive control). Setting: Human reproduction research laboratories. Intervention(S): Fresh semen samples obtained from healthy volunteers after a minimum. of 2 days of sexual abstinence. Main Outcome Measure(s): Protein tyrosine phosphorylation by Western blotting, the acrosomal. status upon binding to the Pisum sativum agglutinin conjugated to fluorescein isothiocyanate, and sperm motility by computerassisted sperm analysis. Results: MIF displayed a dose-dependent effect I on the phosphotyrosine content of p105 and p81, the two major tyrosine-phosphorylated proteins associated with human sperm capacitation. A significant induction of tyrosine I phosphorylation was seen at 2 ng/mL of MIF for both p105 and p81, but a trend for a down-regulation of the basal tyrosine phosphorylation level was noted at elevated concentrations (12 - 24,ng/mL). MIF pretreatment of sperma- 1 tozoa resulted in a dose-dependent change in the acrosome reaction induced by the Ca2+ ionophore A23187. After being increased at 1-4 ng/mL MIF with a statistically significant effect observed at 4 ng/mL, the acrosome reaction gradually decreased and fell below the control levels at higher concentrations. Furthermore, a significant decrease I in the motility of spermatozoa was observed after exposure to an elevated concentration of MIF (12 ng/mL). Conclusion(s): The present data indicate that MIF may play physiological role in sperm capacitation but may have deleterious effects on sperm function at abnormal pathophysiological levels, which suggests a role in endometnosisassociated infertility.