Decreased protein tyrosine phosphorylation and membrane fluidity in spermatozoa from infertile men with varicocele

Abstract

Varicocele is a prevalent pathology among infertile men. The mechanisms linking this condition to infertility, however, are poorly understood. Our previous work showed a relationship between sperm functional quality and the ability of spermatozoa to respond to capacitating conditions with increased membrane fluidity and protein tyrosine phosphorylation. Given the reported association between varicocele, oxidative stress, and sperm dysfunction, we hypothesized that spermatozoa from infertile patients with varicocele might have a combined defect at the level of membrane fluidity and protein tyrosine phosphorylation. Semen samples from infertile patients with and without grade II/III left varicocele were evaluated for motion parameters (computer-assisted semen analysis [CASA]), hyperactivation (CASA), incidence and intensity of protein tyrosine phosphorylation (phosphotyrosine immunofluorescence and western blotting), and membrane fluidity (Laurdan fluorometry), before and after a capacitating incubation (6 hr at 37 degrees C in Ham's F10/BSA, 5% CO(2)). Spermatozoa from varicocele samples presented a decreased response to the capacitating challenge, showing significantly lower motility, hyperactivation, incidence and intensity of tyrosine phosphorylation, and membrane fluidity. The findings reported in this article indicate that the sperm dysfunction associated to infertile varicocele coexists with decreased sperm plasma membrane fluidity and tyrosine phosphorylation. These deficiencies represent potential new pathophysiological mechanisms underlying varicocele-related infertility.

Human sperm anatomy and endocrinology in varicocele: role of androgen receptor

“…This result may probably be due to the reduced expression of AR determining a decreased responsiveness to DHT. Besides, our data are in agreement with the idea that grade II/III infertile varicocele presents an alteration in sperm plasma membrane dynamics due a decreased cholesterol mobility (Buffone et al 2006).…”

High Cholesterol Content and Decreased Membrane Fluidity in Human Spermatozoa Are Associated With Protein Tyrosine Phosphorylation and Functional Deficiencies

“…This deficiency was associated with an impairment in protein tyrosine phosphorylation and an incapacity to develop hyperactivation. An association between inability to increase membrane fluidity during capacitation and tyrosine phosphorylation and functional deficiencies was also observed in pathologic semen samples of patients with asthenozoospermia and varicocele (Buffone et al, 2005; Buffone et al, 2006). Thus, a common theme connecting defects in membrane dynamics and sperm functional quality is evident.…”

Capacitation‐associated changes in membrane fluidity in asthenozoospermic human spermatozoa

“…Immunofluorescence was employed to examine the incidence of tyrosine phosphorylated sperm cells. L90 cells from normozoospermic individuals were incubated for 6 h under capacitating conditions and the percentage of cells showing fluorescence in their tails was measured as previously described (Buffone et al. , 2006).…”

“…In this regards, previous investigations suggested that these cells have membrane fluidity alterations (Ambrosini et al. , 2001, 2003; Buffone et al. , 2005, 2006).…”

“…, 2004). Spermatozoa from the poor quality fraction are functionally and structurally similar to pathological spermatozoa from asthenozoospermic and varicocele samples (Buffone et al. , 2005, 2006).…”