Selenoprotein P is required for mouse sperm development

Selenoprotein P is required for mouse sperm development
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DOI:
10.1095/biolreprod.105.040360
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发表时间:
2005-07-01
影响因子:
3.6
通讯作者:
Burk, RF
Burk, RF
中科院分区:
生物学2区
文献类型:
--
作者:
Olson, GE;Winfrey, VP;Burk, RF

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硒蛋白P(SEPP 1)是一种功能未知的胞外糖蛋白,是硒蛋白家族的独特成员,根据物种的不同,其一级结构中含有10-17个硒代半胱氨酸;相反,所有其他家族成员都含有单个硒代半胱氨酸残基。SEPP 1-null(Sepp 1(-/-))雄性小鼠而非雌性小鼠是不育的,但这种雄性表型的细胞基础尚未确定。在这项研究中,我们证明,成熟的精子Sepp 1(-/-)男性显示一组特定的鞭毛结构缺陷,在精子发生和睾丸成熟后,在附睾的时间发展。鞭毛缺陷包括一个截断的线粒体鞘的发展,一组特定的轴丝微管和外部致密的纤维从主片的挤出,并最终形成发夹状弯曲形成在midpiece-principal片连接。在Sepp 1(-/-)雄性中发现的精子缺陷似乎与在喂食低硒饮食的野生型(Sepp 1(+/+))雄性中观察到的精子缺陷相同。补充Seppl(-/-)男性的膳食硒水平既不能逆转精子缺陷的发展,也不能恢复生育能力。这些数据表明,SEPP 1是功能精子发育所必需的,并表明它是发育生殖细胞的硒递送途径的重要组成部分。
Selenoprotein P (SEPP1), an extracellular glycoprotein of unknown function, is a unique member of the selenoprotein family that, depending on species, contains 10-17 selenocysteines in its primary structure; in contrast, all other family members contain a single selenocysteine residue. The SEPP1-null (Sepp1(-/-)) male but not the female mice are infertile, but the cellular basis of this male phenotype has not been defined. In this study, we demonstrate that mature spermatozoa of Sepp1(-/-) males display a specific set of flagellar structural defects that develop temporally during spermiogenesis and after testicular maturation in the epididymis. The flagellar defects include a development of a truncated mitochondrial sheath, an extrusion of a specific set of axonemal microtubules and outer dense fibers from the principal piece, and ultimately a hairpin-like bend formation at the midpiece-principal piece junction. The sperm defects found in Sepp1(-/-) males appear to be the same as those observed in wildtype (Sepp1(+/+)) males fed a low selenium diet. Supplementation of dietary selenium levels for Seppl(-/-) males neither reverses the development of sperm defects nor restores fertility. These data demonstrate that SEPP1 is required for development of functional spermatozoa and indicate that it is an essential component of the selenium delivery pathway for developing germ cells.