Role of Selenoprotein P in Male Fertility

硒蛋白 P 在男性生育力中的作用

• 批准号: 7236227
• 负责人: GARY E OLSON
• 金额: $ 28.99万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-06 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7236227
• 关键词: Accounting; Affinity; Anabolism; Animals; Antibodies; Binding Proteins; Cell Communication; Cells; Defect; Development; Dietary Selenium; Drug or chemical Tissue Distribution; Electron Microscopy; Enzymes; Epididymis; Epithelium; Exhibits; Fertility; Fiber; Functional disorder; Germ Cells; Glutathione; Gold Colloid; Immunoprecipitation; Infertility; Knockout Mice; Light; Localized; Micronutrients; Mitochondria; Molecular; Organ; Physiological; Plasma; Proteome; Proteomics; Role; Selenium; Selenocysteine; Spermatids; Spermiogenesis; Structure; Supplementation; System; Testing; Testis; Thioredoxin; Tissues; base; cell motility; cell type; extracellular; male; receptor; research study; selenium deficiency; selenoprotein; sperm cell; trafficking; uptake

DESCRIPTION (provided by applicant): Selenium is an essential dietary micronutrient required to maintain male fertility. Selenium exerts its physiological activity through selenoproteins that contain stochiometric amounts of selenium, as selenocysteine, in their primary structure. Epididymal spermatozoa of selenium deficient animals exhibit a loss of motility and display various defects including abnormalities of the mitochondrial sheath and disorganization of the flagellar fibers; our studies demonstrate the defects appear sequentially during spermiogenesis and post-testicular maturation underscoring roles for selenium in both the testis and epididymis. Selenium concentrations of the testis and spermatozoa are higher than other tissues, and the testis maintains its selenium content longer than other organs during dietary selenium deficiency. Thus the testis has a mechanism with which it competes effectively for selenium within the animal to support sperm development. Selenoprotein P (Se-P) is an extracellular selenoprotein that accounts for most of the selenium in plasma. We have produced Se-P null mice and the homozygous males are infertile. Testis selenium levels of Se-P null mice are extremely low and not elevated by selenium supplementation. Spermatids and epididymal spermatozoa of Se-P null animals exhibit structural defects of selenium deficiency. Our central hypothesis is that Se-P provides selenium to specific cell types of the testis and epididymis to support selenoprotein synthesis required for normal sperm development. The specific aims of this study are: Aim 1: To elucidate the potential roles of Se-P in spermiogenesis and post-testicular sperm development by defining its localization in the testis and epididymis. Aim 2: To determine if Se-P provides selenium to the seminiferous and epididymal tubules for biosynthesis of other selenoproteins. Aim 3: To identify and localize Se-P-binding proteins in the testis and epididymis. Aim 4: To determine the molecular basis for sperm defects in Se-P null mice.

描述（由申请人提供）：硒是维持男性生育能力所需的必不可少的饮食微量营养素。硒通过硒蛋白在其主要结构中通过硒含量（如硒代半胱氨酸）发挥其生理活性。硒缺陷动物的附睾精子表现出运动能力的丧失，并表现出各种缺陷，包括线粒体鞘的异常以及鞭毛纤维的混乱。我们的研究表明，在睾丸和附加膜中，硒的精子发生和硒的生理后成熟作用，依次出现缺陷。睾丸和精子的硒浓度高于其他组织，并且在饮食中硒缺乏期间，睾丸的硒含量比其他器官更长。因此，睾丸具有一种机制，它在动物内有效竞争了支持精子发育的机制。硒蛋白P（SE-P）是一种细胞外硒蛋白，占血浆中大部分硒。我们已经产生了se-p null小鼠，纯合雄性是不育的。睾丸硒水平的Se-p Null小鼠非常低，并未因补充硒而升高。 Se-p Null动物的精子和附子精子表现出硒缺乏的结构缺陷。我们的中心假设是，SE-P为睾丸和附睾的特定细胞类型提供了硒，以支持正常精子发育所需的硒蛋白合成。这项研究的具体目的是： 目的1：通过定义其在睾丸和附睾中的定位，阐明SE-P在精子发生和新生后精子发育中的潜在作用。 目标2：确定SE-P是否为其他硒蛋白的生物合成的生物合成提供了硒。 目标3：在睾丸和附睾中识别和定位SE-P结合蛋白。 目标4：确定Se-P Null小鼠精子缺陷的分子基础。