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

ObjectiveTo evaluate the effect of macrophage migration inhibitory factor (MIF) on sperm capacitation, a maturational process that occurs in the female reproductive tract and enables spermatozoa to become fully competent at fertilizing the oocyte.DesignIncubation of Percoll-washed spermatozoa with varying concentrations of human recombinant MIF or fetal cord serum (positive control).SettingHuman 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 computer-assisted sperm analysis.ResultsMIF displayed a dose-dependent effect on the phosphotyrosine content of p105 and p81, the two major tyrosine-phosphorylated proteins associated with human sperm capacitation. A significant induction of tyrosine 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 spermatozoa 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 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 a physiological role in sperm capacitation but may have deleterious effects on sperm function at abnormal pathophysiological levels, which suggests a role in endometriosis-associated infertility.