Buffone M G, Brugo-Olmedo S, Calamera J C, Verstraeten S V, Urrutia F, Grippo L, Corbetta J P, Doncel G F
Laboratorio de Estudios en Reproducción, LER, Buenos Aires, Argentina.
Mol Reprod Dev. 2006 Dec;73(12):1591-9. doi: 10.1002/mrd.20611.
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.
精索静脉曲张是不育男性中普遍存在的一种病理状况。然而,将这种病症与不育联系起来的机制却鲜为人知。我们之前的研究表明,精子功能质量与精子在获能条件下通过增加膜流动性和蛋白质酪氨酸磷酸化做出反应的能力之间存在关联。鉴于精索静脉曲张、氧化应激与精子功能障碍之间已报道的关联,我们推测患有精索静脉曲张的不育患者的精子可能在膜流动性和蛋白质酪氨酸磷酸化水平上存在联合缺陷。对患有和未患有II/III级左侧精索静脉曲张的不育患者的精液样本,在获能孵育(37℃于Ham's F10/牛血清白蛋白中孵育6小时,5%二氧化碳)前后,评估其运动参数(计算机辅助精液分析[CASA])、超活化(CASA)、蛋白质酪氨酸磷酸化的发生率和强度(磷酸酪氨酸免疫荧光和蛋白质印迹法)以及膜流动性(劳丹荧光测定法)。来自精索静脉曲张样本的精子对获能刺激的反应降低,表现为活力、超活化、酪氨酸磷酸化的发生率和强度以及膜流动性显著降低。本文报道的研究结果表明,与不育性精索静脉曲张相关的精子功能障碍与精子质膜流动性降低和酪氨酸磷酸化并存。这些缺陷代表了精索静脉曲张相关性不育潜在的新病理生理机制。