关键词: GGCX Tmem16a Trpv6 calcium homeostasis epididymis luminal microenvironment matrix gla protein (MGP) sperm maturation

来  源:   DOI:10.3389/fcell.2022.827940   PDF(Pubmed)

Abstract:
In the male reproductive tract, the epididymis is an essential organ for sperm maturation, in which sperm cells acquire mobility and the ability to fertilize oocytes while being stored in a protective microenvironment. Epididymal function involves a specialized luminal microenvironment established by the epithelial cells of epididymal mucosa. Low-calcium concentration is a unique feature of this epididymal luminal microenvironment, its relevance and regulation are, however, incompletely understood. In the rat epididymis, the vitamin D-related calcium-dependent TRPV6-TMEM16A channel-coupler has been shown to be involved in fluid transport, and, in a spatially complementary manner, vitamin K2-related γ-glutamyl carboxylase (GGCX)-dependent carboxylation of matrix Gla protein (MGP) plays an essential role in promoting calcium-dependent protein aggregation. An SNP in the human GGCX gene has been associated with asthenozoospermia. In addition, bioinformatic analysis also suggests the involvement of a vitamin B6-axis in calcium-dependent MGP-mediated protein aggregation. These findings suggest that vitamins interact with calcium homeostasis in the epididymis to ensure proper sperm maturation and male fertility. This review article discusses the regulation mechanisms of calcium homeostasis in the epididymis, and the potential role of vitamin interactions on epididymal calcium homeostasis, especially the role of matrix calcium in the epididymal lumen as a cofactor for the carboxylated MGP-mediated scavenging function.
摘要:
在男性生殖道,附睾是精子成熟的重要器官,其中精子细胞获得流动性和受精卵母细胞的能力,同时储存在保护性微环境中。附睾功能涉及由附睾粘膜上皮细胞建立的专门的腔微环境。低钙浓度是这种附睾腔微环境的独特特征,它的相关性和监管是,然而,不完全理解。在大鼠附睾中,维生素D相关的钙依赖性TRPV6-TMEM16A通道耦合剂已被证明参与液体运输,and,以空间互补的方式,维生素K2相关的γ-谷氨酰羧化酶(GGCX)依赖性基质Gla蛋白(MGP)的羧化作用在促进钙依赖性蛋白质聚集中起重要作用。人类GGCX基因中的SNP与弱精子症有关。此外,生物信息学分析也提示维生素B6轴参与钙依赖性MGP介导的蛋白质聚集.这些发现表明,维生素与附睾中的钙稳态相互作用,以确保适当的精子成熟和男性生育能力。这篇综述文章讨论了附睾钙稳态的调节机制,以及维生素相互作用对附睾钙稳态的潜在作用,尤其是基质钙在附睾腔中作为羧化MGP介导的清除功能的辅因子的作用。
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