Store-operated calcium entry (SOCE) is an important Ca(2+) influx pathway in somatic cells. In addition to maintaining endoplasmic reticulum (ER) Ca(2+) stores, Ca(2+) entry through store-operated channels regulates essential signaling pathways in numerous cell types. Patients with mutations in the store-operated channel subunit ORAI1 exhibit defects in store-operated Ca(2+) influx, along with severe immunodeficiency, congenital myopathy and ectodermal dysplasia. However, little is known about the functional role of ORAI1 in germ cells and reproductive function in mice, or in men, since men with loss-of-function or null mutations in ORAI1 rarely survive to reproductive age. In this study, we investigated the role of ORAI1 in male reproductive function. We reveal that Orai1(-/-) male mice are sterile and have severe defects in spermatogenesis, with prominent deficiencies in mid- to late-stage elongating spermatid development. These studies establish an essential in vivo role for store-operated ORAI1 channels in male reproductive function and identify these channels as potential non-steroidal regulators of male fertility.

中文翻译：

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缺少存储操作的Ca（2+）通道Orai1的小鼠中的男性不育。

存储操作钙进入（SOCE）是体细胞中重要的Ca（2+）流入途径。除了维持内质网（ER）Ca（2+）存储外，通过存储操作通道的Ca（2+）进入还可以调节多种细胞类型中的必需信号通路。具有存储操作的通道亚基ORAI1突变的患者在存储操作的Ca（2+）涌入中显示缺陷，以及严重的免疫缺陷，先天性肌病和外胚层发育不良。但是，关于ORAI1在小鼠或男性生殖细胞和生殖功能中的功能作用知之甚少，因为ORAI1中功能丧失或无效突变的男性很少能存活到生殖年龄。在这项研究中，我们调查了ORAI1在男性生殖功能中的作用。我们发现Orai1（-/-）雄性小鼠不育，在精子发生中有严重缺陷，在中晚期精子细胞延长发育中存在明显缺陷。这些研究为男性生殖功能中存储操作的ORAI1通道确立了体内必不可少的作用，并将这些通道确定为男性生育力的潜在非甾体调节剂。