Olson Gary E, Winfrey Virginia P, Nagdas Subir K, Hill Kristina E, Burk Raymond F
Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee 37232, USA.
Biol Reprod. 2005 Jul;73(1):201-11. doi: 10.1095/biolreprod.105.040360. Epub 2005 Mar 2.
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 wild-type (Sepp1(+/+)) males fed a low selenium diet. Supplementation of dietary selenium levels for Sepp1(-/-) 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.
硒蛋白P（SEPP1）是一种功能未知的细胞外糖蛋白，是硒蛋白家族的独特成员，根据物种不同，其一级结构中含有10 - 17个硒代半胱氨酸；相比之下，所有其他家族成员都只含有一个硒代半胱氨酸残基。SEPP1基因敲除（Sepp1(-/-)）的雄性小鼠不育，而雌性小鼠则正常，但这种雄性表型的细胞基础尚未明确。在本研究中，我们证明Sepp1(-/-)雄性小鼠的成熟精子表现出一组特定的鞭毛结构缺陷，这些缺陷在精子发生过程中以及附睾中睾丸成熟后随时间发展。鞭毛缺陷包括线粒体鞘截断、一组特定的轴丝微管和外致密纤维从主段挤出，最终在中段 - 主段连接处形成发夹样弯曲。在Sepp1(-/-)雄性小鼠中发现的精子缺陷似乎与喂食低硒饮食的野生型（Sepp1(+/+)）雄性小鼠中观察到的缺陷相同。给Sepp1(-/-)雄性小鼠补充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SEPP1是功能性精子发育所必需的，并表明它是发育中的生殖细胞硒传递途径的重要组成部分。
