Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, CP, México.
J Cell Physiol. 2018 Jun;233(6):4735-4747. doi: 10.1002/jcp.26262. Epub 2018 Jan 4.
The sperm acrosome reaction (AR), an essential event for mammalian fertilization, involves Ca permeability changes leading to exocytosis of the acrosomal vesicle. The acrosome, an intracellular Ca store whose luminal pH is acidic, contains hydrolytic enzymes. It is known that acrosomal pH (pH ) increases during capacitation and this correlates with spontaneous AR. Some AR inducers increase intracellular Ca concentration ([Ca ] ) through Ca release from internal stores, mainly the acrosome. Catsper, a sperm specific Ca channel, has been suggested to participate in the AR. Curiously, Mibefradil and NNC55-0396, two CatSper blockers, themselves elevate [Ca ] by unknown mechanisms. Here we show that these compounds, as other weak bases, can elevate pH , trigger Ca release from the acrosome, and induce the AR in both mouse and human sperm. To our surprise, μM concentrations of NNC55-0396 induced AR even in nominally Ca free media. Our findings suggest that alkalization of the acrosome is critical step for Ca release from the acrosome that leads to the acrosome reaction.
精子顶体反应 (AR) 是哺乳动物受精的一个必要事件，涉及钙通透性变化，导致顶体小泡的胞吐作用。顶体是细胞内钙储存库，其腔室 pH 值呈酸性，含有水解酶。已知顶体 pH 值（pH 值）在获能过程中增加，这与自发的 AR 相关。一些 AR 诱导剂通过从内部储存库（主要是顶体）释放 Ca 来增加细胞内 Ca 浓度 ([Ca ])。已经有研究表明，精子特异性钙通道 Catsper 参与了 AR。奇怪的是，两种 CatSper 阻断剂米贝地尔和 NNC55-0396 通过未知机制本身也会升高 [Ca ]。在这里，我们表明这些化合物，如同其他弱碱基一样，可以升高 pH 值，引发顶体中的 Ca 释放，并在小鼠和人精子中诱导 AR。令我们惊讶的是，NNC55-0396 的 μM 浓度甚至可以在名义上无 Ca 的培养基中诱导 AR。我们的研究结果表明，顶体的碱化是 Ca 从顶体释放并导致顶体反应的关键步骤。
