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 (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.


METHODS
Incubation of Percoll-washed spermatozoa with varying concentrations of human recombinant MIF or fetal cord serum (positive control).


METHODS
Human reproduction research laboratories.


METHODS
Fresh semen samples obtained from healthy volunteers after a minimum of 2 days of sexual abstinence.


METHODS
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.


RESULTS
MIF 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 Ca(2+) 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).


CONCLUSIONS
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.
Carli
Cédric
C
Endocrinologie de la Reproduction, Centre de Recherche, Hôpital Saint-François d'Assise, Centre Hospitalier Universitaire de Québec (CHUQ), Faculté de Médecine, Université Laval, Québec, Canada.
Leclerc
Pierre
P
Metz
Christine N
CN
Akoum
Ali
A
D004305:Dose-Response Relationship, Drug; D004715:Endometriosis / Q000209:etiology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007247:Infertility, Female / Q000209:etiology / Q000378:metabolism*; D008263:Macrophage Migration-Inhibitory Factors / Q000009:adverse effects / Q000494:pharmacology* / Q000502:physiology; D008297:Male; D013075:Sperm Capacitation / Q000502:physiology*; D013094:Spermatozoa / Q000502:physiology*
D008263:Macrophage Migration-Inhibitory Factors