EFFECTS OF AGING ON THE EPIDIDYMIS

精子成熟后储存在附睾处。虽然 了解这种组织在发育和发育过程中是如何被调节的 在成人成长过程中，人们对发生的变化知之甚少 随着男性年龄的增长，在这个组织中。年迈的棕色挪威鼠提供 没有研究生殖系统老化的机会 由于同时发生的病变而导致的复杂性。这个 该项目的长期目标是了解潜在的 附睾部发生改变的机制 随着动物年龄的增长。我们的基本假设是，成年人 附睾上皮细胞衰老独立于 腔室内精子的存在，因此 独立于正常运作的睾丸。为了测试这一点 根据这一假设，将采取四种互补的办法。这个 首先是确定S的细胞和生理意义 附睾腺的形态变化 衰老。我们将研究的可能机制包括 氧化应激增加，细胞间相互作用的改变，以及 溶酶体活性增强。第二种方法是解决 如何调节衰老过程中选择性的生化变化；我们 将重点放在附睾5α还原酶的控制上 与细胞凋亡相关的蛋白质。第三种方法是 以确定衰老如何影响生育力和功能 附睾精子的特征。活体生育力研究 将进行体外受精研究；功能改变 精子的解凝集方式和DNA 将对模板功能进行评估。最后一种方法是 确定内分泌如何影响与年龄相关的变化 和/或旁分泌因子。老化的后果对 睾丸切除和睾酮替代，改变睾丸输入 附睾术，输精管结扎术对附睾部结构的影响 并对其功能进行了研究。总而言之，这些研究不仅将 提供有关导致该组织 年龄，但也可能提供关于老年人衰老过程的新见解 非潜水细胞。

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.