Adenylate kinase 1 deficiency disrupts mouse sperm motility under conditions of energy stress
Adenylate kinase 1 deficiency disrupts mouse sperm motility under conditions of energy stress
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DOI：
10.1093/biolre/ioaa134
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发表时间：
2020-11-01
影响因子：
3.6
通讯作者：
Chen, Zhenguo
中科院分区：
文献类型：
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作者：
Xie, Minyu;Zhang, Guofei;Chen, Zhenguo
哺乳动物精子是高度极化的细胞，其特征在于细胞结构和能量代谢的区室化。腺苷酸激酶（AK）将两个ADP分子相互转化为化学计量量的ATP和AMP，在缓冲整个尾部的腺嘌呤核苷酸以支持鞭毛运动中起关键作用。然而，主要的AK亚型AK 1的作用仍然没有得到很好的表征。在这里，通过使用睾丸活检样本的蛋白质组学分析，我们发现AK 1水平显着降低非梗阻性无精子症患者。该结果通过组织芯片上AK 1的免疫组织化学染色进一步验证。AK 1在小鼠睾丸中减数分裂后的圆形和细长的精子细胞以及随后的附睾中的成熟精子中表达。然后，我们产生Akl敲除小鼠，这表明AK 1缺乏不会诱导生理条件下睾丸发育、精子发生或精子形态和活力的任何缺陷。我们进一步研究了洗涤剂模拟的附睾精子，并包括单独或混合的腺嘌呤核苷酸来模拟能量应激。当只有ADP可用时，Akl破坏在很大程度上损害了精子活力，表现为较小的跳动幅度和较高的跳动频率，这导致不太有效的向前游泳。用完整精子进行的能量限制/恢复实验进一步证实了这一发现。此外，在氯化镉诱导的雄性生育障碍小鼠模型中观察到精子AK活性降低。这些结果累积表明，AK 1是睾丸发育，精子发生，或精子活力在生理条件下，但需要精子保持恒定的腺苷酸能量电荷，以支持精子活力在能量应激条件下。
Mammalian spermatozoa are highly polarized cells characterized by compartmentalized cellular structures and energy metabolism. Adenylate kinase (AK), which interconverts two ADP molecules into stoichiometric amounts of ATP and AMP, plays a critical role in buffering adenine nucleotides throughout the tail to support flagellar motility. Yet the role of the major AK isoform, AK1, is still not well characterized. Here, by using a proteomic analysis of testis biopsy samples, we found that AK1 levels were significantly decreased in nonobstructive azoospermia patients. This result was further verified by immunohistochemical staining of AK1 on a tissue microarray. AK1 was found to be expressed in post-meiotic round and elongated spermatids in mouse testis and subsequent mature sperm in the epididymis. We then generated Akl knockout mice, which showed that AK1 deficiency did not induce any defects in testis development, spermatogenesis, or sperm morphology and motility under physiological conditions. We further investigated detergent-modeled epididymal sperm and included individual or mixed adenine nucleotides to mimic energy stress. When only ADP was available, Akl disruption largely compromised sperm motility, manifested as a smaller beating amplitude and higher beating frequency, which resulted in less effective forward swimming. The energy restriction/recover experiments with intact sperm further addressed this finding. Besides, decreased AK activity was observed in sperm of a male fertility disorder mouse model induced by cadmium chloride. These results cumulatively demonstrate that AK1 was dispensable for testis development, spermatogenesis, or sperm motility under physiological conditions, but was required for sperm to maintain a constant adenylate energy charge to support sperm motility under conditions of energy stress.