Research Group of Intracellular Signalling and Technology of Reproduction, Veterinary School, University of Extremadura, Caceres, Spain.
PLoS One. 2012;7(6):e38840. doi: 10.1371/journal.pone.0038840. Epub 2012 Jun 14.
The main functions of spermatozoa required for fertilization are dependent on the energy status and metabolism. AMP-activated kinase, AMPK, acts a sensor and regulator of cell metabolism. As AMPK studies have been focused on somatic cells, our aim was to investigate the expression of AMPK protein in spermatozoa and its possible role in regulating motility. Spermatozoa from boar ejaculates were isolated and incubated under different conditions (38,5°C or 17°C, basal medium TBM or medium with Ca(2+) and bicarbonate TCM, time from 1-24 hours) in presence or absence of AMPK inhibitor, compound C (CC, 30 µM). Western blotting reveals that AMPK is expressed in boar spermatozoa at relatively higher levels than in somatic cells. AMPK phosphorylation (activation) in spermatozoa is temperature-dependent, as it is undetectable at semen preservation temperature (17°C) and increases at 38,5°C in a time-dependent manner. AMPK phosphorylation is independent of the presence of Ca(2+) and/or bicarbonate in the medium. We confirm that CC effectively blocks AMPK phosphorylation in boar spermatozoa. Analysis of spermatozoa motility by CASA shows that CC treatment either in TBM or in TCM causes a significant reduction of any spermatozoa motility parameter in a time-dependent manner. Thus, AMPK inhibition significantly decreases the percentages of motile and rapid spermatozoa, significantly reduces spermatozoa velocities VAP, VCL and affects other motility parameters and coefficients. CC treatment does not cause additional side effects in spermatozoa that might lead to a lower viability even at 24 h incubation. Our results show that AMPK is expressed in spermatozoa at high levels and is phosphorylated under physiological conditions. Moreover, our study suggests that AMPK regulates a relevant function of spermatozoa, motility, which is essential for their ultimate role of fertilization.
精子受精所需的主要功能依赖于能量状态和代谢。 AMP 激活的蛋白激酶(AMPK)作为细胞代谢的传感器和调节剂。由于 AMPK 的研究主要集中在体细胞上,我们的目的是研究 AMPK 蛋白在精子中的表达及其在调节运动性中的可能作用。从猪精液中分离精子,并在不同条件下(38.5°C 或 17°C、基础培养基 TBM 或含有 Ca(2+)和碳酸氢盐的 TCM、从 1 到 24 小时的时间)孵育,同时存在或不存在 AMPK 抑制剂化合物 C(CC,30µM)。Western blot 分析显示,AMPK 在猪精子中的表达水平相对高于体细胞。精子中 AMPK 的磷酸化(激活)依赖于温度,在精液保存温度(17°C)下无法检测到,并且在 38.5°C 时呈时间依赖性增加。AMPK 磷酸化与培养基中是否存在 Ca(2+)和/或碳酸氢盐无关。我们证实 CC 可有效阻断猪精子中 AMPK 的磷酸化。通过 CASA 分析精子运动性,发现 CC 处理无论是在 TBM 还是在 TCM 中,都可导致精子任何运动参数随时间的推移显著降低。因此,AMPK 抑制以时间依赖性方式显著降低了运动和快速精子的百分比,显著降低了精子速度 VAP、VCL,并影响了其他运动参数和系数。CC 处理在 24 小时孵育时不会对精子造成额外的副作用,即使在 24 小时孵育时也不会导致精子活力降低。我们的结果表明,AMPK 在精子中高表达,并在生理条件下磷酸化。此外,我们的研究表明,AMPK 调节精子的一个重要功能,即运动性,这对其最终的受精作用至关重要。