Lysophosphatidic Acid Improves Human Sperm Motility by Enhancing Glycolysis and Activating L-Type Calcium Channels.
Lysophosphatidic Acid Improves Human Sperm Motility by Enhancing Glycolysis and Activating L-Type Calcium Channels.
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溶血磷脂酸通过增强糖酵解和激活 L 型钙通道来提高人类精子活力
DOI：
10.3389/fendo.2022.896558
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发表时间：
2022
影响因子：
5.2
通讯作者：
Zhou, Yuchuan
中科院分区：
文献类型：
--
作者：
Li, Yinlam;Jin, Li;Li, Yanquan;Qian, Jianing;Wang, Zhengquan;Zheng, Xiaoguo;Xie, Chong;Zhang, Xuelian;Huang, Hefeng;Zhou, Yuchuan
到目前为止，人们对精子活力缺陷导致男性不育的分子机制仍知之甚少。能够提高精子活力的安全有效的化合物或药物也非常有限。溶血磷脂酸（LPA）是一种天然存在的磷脂，是一种具有多种生物活性的生物活性中间体。已在卵巢癌患者的血清、血浆、唾液、眼泪、疱液、鸡蛋清和腹水中等各种体液中检测到它。 LPA在精浆和卵泡液中也含量丰富。它增强卵泡刺激，改善卵母细胞受精，促进早期胚胎发育和胚胎植入。然而，LPA 在男性生殖系统中的生理作用仍不清楚。在这里，我们的研究表明，LPA 以剂量依赖性方式显着改善人类精子过度活跃的运动参数。 LPA 诱导的精子活力升高依赖于牛血清白蛋白 (BSA)，但与经典 BSA 诱导的 sAC/cAMP/PKA 信号通路无关。 LPA 对精子活力的增强不能被 CCCP（一种抑制线粒体 ATP 产生的呼吸抑制剂）阻断。此外，LPA 提高了糖酵解中磷酸丙糖异构酶的活性。同时，LPA处理显着增加了精子糖酵解过程中ATP和磷酸烯醇丙酮酸的水平，并降低了ADP的含量。值得注意的是，在人类精子中没有检测到任何已知或已识别的 LPA 受体。进一步的研究表明，LPA通过L型钙通道促进精子活力。总之，本研究揭示了 LPA 通过增强糖酵解和激活 L 型钙通道来参与人类精子活力的调节。目前的研究结果可能为理解弱精子症的原因提供新的线索，并表明LPA可以作为一种新型治疗剂来改善精子功能和受精能力。
Until now, the molecular mechanisms underlining sperm motility defect causing male infertility are still poorly understood. Safe and effective compounds or drugs that can improve sperm motility are also very limited. Lysophosphatidic acid (LPA) is a naturally occurring phospholipid and a bioactive intermediate with multiple biological activities. It has been detected in various body fluids such as serum, plasma, saliva, tears, blister fluids, hen egg white, and ascites from patients with ovarian cancer. LPA is also abundant in seminal plasma and follicular fluid. It enhances follicle stimulation, improves oocyte fertilization, and promotes early embryonic development and embryo implantation. However, the physiological role of LPA in the male reproductive system remains unknown. Here, our study showed that LPA significantly improved the motility parameters of human sperm hyperactivation in a dose-dependent manner. The LPA-induced elevation of sperm motility is dependent on bovine serum albumin (BSA) but independent of the classical BSA-induced sAC/cAMP/PKA signaling pathway. The enhancement of sperm motility by LPA could not be blocked by CCCP, a respiratory inhibitor suppressing mitochondrial ATP production. Moreover, LPA improved the activity of triosephosphate isomerase in glycolysis. Meanwhile, LPA treatment significantly increased ATP and phosphoenolpyruvate levels and decreased ADP content during sperm glycolysis. Notably, none of known or identified LPA receptors was detected in human sperm. Further investigations showed that LPA promoted sperm motility through L-type calcium channels. In summary, this study revealed the involvement of LPA in the regulation for human sperm motility by enhancing glycolysis and activating L-type calcium channels. The current findings may shed new light on the understanding of causes of asthenozoospermia, and indicate that LPA could be used as a novel therapeutic agent to improve sperm function and fertilizing capacity.
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