Fibronectin modulates the endocannabinoid system through the cAMP/PKA pathway during human sperm capacitation

MARTÍNEZ-LEÓN, EDUARDO; OSYCKA-SALUT, CLAUDIA; SIGNORELLI, JANETTI; KONG, MILENE; MORALES, PATRICIO; PÉREZ-MARTÍNEZ, SILVINA; DÍAZ, EMILCE SILVINA

MOLECULAR REPRODUCTION AND DEVELOPMENT

WILEY-LISS, DIV JOHN WILEY & SONS INC

Lugar: New York; Año: 2018

1040-452X

Fibronectin (Fn) enhances human sperm capacitation via the cAMP/PKA pathway, and the endocannabinoid system participates in this process. Moreover, Fn has been linked to endocannabinoid system components in different cellular models, even though no evidence of such interactions in human sperm is available. Normal semen samples were evaluated over a four-year period. Our findings suggest that (i) the capacitating effects of Fn were reversed by pre-incubating the sperm with a cannabinoid receptor 1 (CB1) or transient receptor potential cation channel subfamily V member 1 (TRPV1) antagonist (P<0.001 and P<0.05, respectively); (ii) cooperation between CB1 and TRPV1 may exist (P<0.01); (iii) the activity of specific fatty acid amide hydroxylase (FAAH) decreased after 1 min (P<0.01) and increased after 60 min (P<0.01) of capacitation in the presence of Fn; (iv) the effects of Fn on FAAH activity were prevented by pre-incubating spermatozoa with a PKA inhibitor (P<0.01); (v) Fn modulated both the cAMP concentration and PKA activity (P<0.05) during early capacitation; and (vi) FAAH was a PKA substrate modulated by phosphorylation. These findings indicate that Fn stimulates human sperm capacitation via the cAMP/PKA pathway through modulation of the endocannabinoid system. Understanding the functional competence of human spermatozoa is essential for facilitating clinical advances in infertility treatment and for developing novel contraceptive strategies.