BIOLOGY OF THE AGING HUMAN TESTIS

人类衰老睾丸的生物学

• 批准号: 3070602
• 负责人: LARRY JOHNSON
• 金额: $ 6.91万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-04-05 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3070602
• 关键词: DNA repair; Leydig cells; Sertoli cells; aging; androgens; autoradiography; blood testis barrier; cyclic AMP; electron microscopy; follicle stimulating hormone; gene expression; high performance liquid chromatography; hormone regulation /control mechanism; human tissue; in situ hybridization; luteinizing hormone; meiosis; microscopy; morphology; nucleic acid hybridization; plasminogen activator; radioimmunoassay; spermatogenesis; testis; testosterone

Our studies have shown that age accounts for a significant portion of testicular variation in normal men, but much of the variation in human spermatogenesis remains to be explained. The long-term objective is to understand the variation in human spermatogenesis and its age-related reduction. The specific aims are to relate the variation in daily sperm production to: the architecture of tubules in terms of size and distribution of stages; stage-dependency of protein and RNA synthesis in Sertoli cells; DNA repair capacity of Sertoli cells or spermatogonia; biochemical composition of tubular boundary tissue; status of the blood testis barrier and amount of plasminogen activator in degenerative tubules; gene expression and chromosomal status of spermatocytes known to degenerate in aging men; in vitro production of androgens; and serum concentrations of FSH, LH, and testosterone. The experimental design for achieving these goals includes the use of autopsy specimens from men 20 to 94 years old and fresh specimens obtained from men aged 50 to 90 years undergoing elective orchidectomy for prostatic carcinoma. The unavailability of fresh specimens from young men necessitates the use of spermatogenically active testes from older men. The methods to be used include three-dimensional reconstruction of human seminiferous tubules; testicular stereology; testicular cell counts; autoradiography; radioimmunoassay; high performance liquid chromatography; chromosomal analysis; in vitro production of proteins, RNA, and androgens; and germ cell isolation by centrifugal elutriation followed by mRNA isolation and hybridization and in situ hybridization to evaluate the relationship between spermatocyte development or degeneration and gene expression during meioses. This project will lead to a better understanding of molecular mechanisms that influence human spermatogenesis and its age-related dysfunction.

我们的研究表明，年龄占很大一部分 正常男性的睾丸变异，但人类的大部分变异 精子发生仍有待解释。 长期目标是 了解人类精子发生的变化及其与年龄的关系 减少。 具体目标是将每日精子的变化联系起来 生产： 管的结构在尺寸和 阶段分布；蛋白质和RNA合成的阶段依赖性 支持细胞；支持细胞或精原细胞的DNA修复能力； 肾小管边界组织的生化成分；血液状态 退行性睾丸屏障和纤溶酶原激活剂的量 肾小管；已知精母细胞的基因表达和染色体状态 老年男性退化；体外产生雄激素；和血清 FSH、LH 和睾酮的浓度。 实验设计为 实现这些目标包括使用男性尸检标本20 至 94 岁以及从 50 至 90 岁男性获得的新鲜标本 因前列腺癌接受选择性睾丸切除术。 这 由于无法获得年轻人的新鲜样本，因此需要使用 老年男性生精活跃的睾丸。 使用的方法 包括人体曲细精管的三维重建； 睾丸体视学；睾丸细胞计数；放射自显影； 放射免疫分析；高效液相色谱法；染色体 分析;蛋白质、RNA 和雄激素的体外生产；和细菌 通过离心淘洗分离细胞，然后分离 mRNA 杂交和原位杂交来评估关系 精母细胞发育或变性与基因表达之间 减数分裂期间。 该项目将有助于人们更好地了解分子 影响人类精子发生的机制及其与年龄相关的 功能障碍。