EFFECTS OF AGING ON THE EPIDIDYMIS

精子成熟后储存在附睾中。 虽然 了解这种组织在发育过程中是如何调节的， 在成年人的成长，很少有人知道的变化， 在这个组织中的变化。老布朗挪威鼠提供了 研究生殖系统老化的机会， 并发病理变化的复杂性。 的 本项目的长期目标是了解 附睾发生变化的机制 随着动物年龄的增长。 我们的基本假设是， 附睾上皮细胞的老化与其细胞的老化无关。 腔室中存在精子，因此 独立于正常功能的睾丸。 为了验证这一 假设，将采取四种互补的办法。 的 首先是确定细胞和生理意义的 我们在附睾中发现的形态学变化， 衰老 我们将研究的可能机制包括 氧化应激增加，细胞间相互作用改变， 增加溶酶体活性。 第二种方法是解决 衰老过程中的选择性生化变化是如何调节的;我们 将集中在附睾5 α-还原酶的控制和 与凋亡性细胞死亡相关的蛋白质。 第三种方法是 以确定衰老如何影响生育能力和功能 附睾精子的特征。 体内生育力研究 进行体外授精研究;功能改变 如精子的解凝聚模式和DNA 将评估模板功能。 最后一种方法是 确定与年龄相关的变化如何受到内分泌的影响 和/或旁分泌因子。 老龄化对人口影响的后果 睾丸切除术和睾酮替代，改变睾丸输入 附睾结构上的输出管结扎 功能将被研究。 这些研究不仅将 提供有关导致这种组织的因素的具体知识， 年龄，但也可能提供有关衰老过程的新见解， 非潜水牢房

Spermatozoa are matured and stored in the epididymis. Although knowledge of how this tissue is regulated during development and in the adult is growing, little is known about changes that take place within this tissue as males age. The aging Brown Norway rat offers the opportunity to study aging of the reproductive system without complexities consequent to simultaneous pathological changes. The long-term objective of this project is to understand the underlying mechanisms responsible for the change that occur in the epididymis as animals age. Our underlying hypothesis is that the adult epididymal epithelium exhibits cellular aging independently of the presence of spermatozoa in the luminal compartment and thus independently of a normally functioning testis. To test this hypothesis, four complementary approaches will be pursued. The first is to determine the cellular and physiological implication s of the morphological changes we have found in the epididymis during aging. Possible mechanisms which we will examine include increased oxidative stress, alterations in cell-cell interactions, and increased lysosomal activity. The second approach is to resolve how selective biochemical changes during aging are regulated; we will focus on the control of epididymal 5alpha-reductases and on proteins associated with apoptotic cell death. The third approach is to identify how aging affects the fertility and the functional characteristics of epididymal spermatozoa. In vivo fertility studies and in vitro insemination studies will be done; functional alterations in spermatozoa such as their decondensation pattern and DNA template functions will be assessed. The final approach is to determine how age associated changes are affected by endocrine and/or paracrine factors. Consequences of aging on the effect of orchidectomy and testosterone replacement, altered testicular input to the epididymis, and efferent duct ligation on epididymal structure and function will be studied. Together, these studies will not only provide specific knowledge about factors that cause this tissue to age, but may also provide new insight about the aging process of non-diving cells.