EFFECTS OF AGING ON THE EPIDIDYMIS

在哺乳动物中，附睾是精子成熟（获得）的部位。 施肥能力）并储存起来。 尽管我们的成长 关于附睾的作用和如何作用的知识， 没有努力确定该组织如何受到影响 通过老化的过程。 老年布朗挪威鼠提供了独特的 研究生殖系统老化的机会， 其他组织同时发生病理变化的复杂性 特别是脑垂体和肝脏。 长期 本项目的目的是确定附睾如何变化， 动物年龄 主要目标是确定（1） 衰老影响特定的形态和功能特征 附睾，以及2）是否与年龄相关的变化是介导的 通过内分泌或旁分泌机制。 为了实现第一个目标，三 将采用补充办法。 对于这三个，附睾 将研究3 - 30个月大的Brown Norway大鼠。 第一种方法 是确定组织的主要组织学特征是如何 受年龄的影响。 第二种方法是使用选择性生化 附睾功能标记物，以评估组织的哪些方面 影响。 北方和西方印迹分析，酶测定和 免疫细胞化学将用于检查发生在4-烯 类固醇5 α-还原酶和雄激素受体，上皮钙粘蛋白， immobilia，硫酸化糖蛋白-2，酸性附睾糖蛋白， 谷胱甘肽S-转移酶和脑啡肽原。 第三种方法是 评估动物的生育能力，因为他们的年龄，并将其与 睾丸和附睾发生的变化。 第二主 本应用程序的目标也将通过执行三种类型的 旨在隔离内分泌和旁分泌影响的操作 附睾上的因素。 三种手法分别是腰椎间盘切除术， 输出管结扎和类固醇治疗旨在改变特定的 睾丸细胞类型。 这些研究将首次提供 详细研究了老化对附睾结构的影响， 功能 老化对这个组织的影响是否是内在的， 它或继发于睾丸中发生的事件也将是 测定

The epididymis is the site, in mammals, where spermatozoa mature (acquire the ability to fertilize) and are stored. In spite of our growing knowledge about what the epididymis does and how it does it, virtually no effort has been invested in determining how this tissue is affected by the process of aging. The aging Brown Norway rat offers the unique opportunity of studying aging of the reproductive system without the complexities consequent to simultaneous pathological changes in other systems, most notably the pituitary and the liver. The long-term objective of this project is to determine how the epididymis changes as animals age. The major goals are to determine 1) how the process of aging affects specific morphological and functional characteristics of the epididymis, and 2) whether the age-associated changes are mediated by endocrine or paracrine mechanisms. To attain the first goal, three complementary approaches will be used. For all three, the epididymides of 3-30 month-old Brown Norway rats will be studied. The first approach is to determine how the major histological features of the tissues are affected by age. The second approach is to use selective biochemical markers of epididymal function to assess which facets of the tissue are affected. Northern and Western blot analyses, enzyme assays and immunocytochemistry will be used to examine changes taking place in 4-ene steroid 5a-reductase, and androgen receptor, epithelial cadherin, immobilia, sulfated glycoprotein-2, acidic epididymal glycoprotein, glutathione S-transferases, and proenkephalin. The third approach is to assess the fertility of the animals as they age and relate it to the changes taking place in the testis and the epididymis. The second major goal of this application will also be attained by doing three types of manipulations designed to isolate the impact of endocrine and paracrine factors on the epididymis. The three manipulations are orchidectomy, efferent duct ligation and steroid treatments designed to alter specific testicular cell type(s). Together, these studies will provide the first detailed studies of the consequences of aging on epididymal structure and function. Whether the effects of aging on this tissue are intrinsic to it or secondary to events taking place in the testis will also be determined.