Sperm Survival Versus Degradation in the Mammalian Epididymis: A Hypothesis1

Abstract

A long-standing problem in epididymal physiology is the fate of unejaculated spermatozoa in the cauda epididymidis under conditions such as congenital absence of the vas deferens, long-term vasectomy, or castration. There is no convincing evidence for significant absorption of spermatozoa, defective or otherwise, by spermiophagy or dissolution in the epididymis of normal animals. Spermiophagy by epithelial cells or intraluminal macrophages may take place if the duct ruptures and granulomas form (e.g., after experimental ligation), although there is no quantitative information on the rate of sperm removal by this means. In one animal model (the rabbit), the epididymis is unusually resistant to granuloma formation and has provided unique insights into a phenomenon that is suggested to be present in all species. Spermatozoa retained in the rabbit cauda epididymidis by placing ligatures on the vas deferens and corpus epididymidis degenerate after several weeks but do not decrease significantly in numbers. After castration, however, they die very rapidly and >90% disappear. It is hypothesized that, in the normal androgen-maintained epididymis, degradative pathways are present in the luminal fluid that are constitutively inhibited by survival signals emanating from the epithelium. In the absence of androgen, the intraluminal mileau changes and death signals predominate that activate degradative pathways via the ubiquitin-proteasome system, DNAses, etc., to mediate dissolution of sperm organelles and nucleoprotein. It is suggested that the latter condition is the default situation and is only prevented by the stimulatory action of androgens on the epididymal epithelium.

Alteration of fertility endpoints in adult male F-344 rats by subchronic exposure to inhaled benzo(a)pyrene

“…According to Plant and Marshall (2001), high intratesticular testosterone concentration is required for the regulation of spermatogenesis, the reduction of which results in fewer matured sperm produced by the testis. Furthermore, the reduced concentrations of plasma testosterone among BaP-exposed rats compared with UNC may have caused a rapid regression in the epididymal epithelium, especially in the initial segment and the proximal caput epididymal region (Jones, 2004). As a result, epididymal sperm maturation and survival were adversely affected and during the ensuing weeks, only a few degenerated sperm became present in the cauda epididymides and vas deferens (Jones, 2004).…”

“…Furthermore, the reduced concentrations of plasma testosterone among BaP-exposed rats compared with UNC may have caused a rapid regression in the epididymal epithelium, especially in the initial segment and the proximal caput epididymal region (Jones, 2004). As a result, epididymal sperm maturation and survival were adversely affected and during the ensuing weeks, only a few degenerated sperm became present in the cauda epididymides and vas deferens (Jones, 2004). Raychoudhury and Kubinski (2003) reported that in vitro exposure of isolated rat Sertoli cells to BaP resulted in cellular changes characteristic of apoptosis.…”

“…The reduction in the percentage of normal morphologic forms of spermatozoa may be related to BaP-induced reduction of testosterone synthesis and release. If BaP reduces intra-testicular steroidogenesis substantially during sub-chronic exposure, the level of testosterone reaching the epididymides from general circulation and testicular fluid (Jones, 2004) may not be sufficient to optimally regulate the epididymides. This scenario could lead to a significant reduction in sperm maturation, survival and ultimately to the presence of degenerated spermatozoa in the cauda epididymides and vas deferens (Jones, 2004).…”

“…If BaP reduces intra-testicular steroidogenesis substantially during sub-chronic exposure, the level of testosterone reaching the epididymides from general circulation and testicular fluid (Jones, 2004) may not be sufficient to optimally regulate the epididymides. This scenario could lead to a significant reduction in sperm maturation, survival and ultimately to the presence of degenerated spermatozoa in the cauda epididymides and vas deferens (Jones, 2004). The increased percentage of decapitated spermatozoa in the cauda epididymides of BaP-exposed rats compared with UNC could be likened to the degenerating conditions of stored spermatozoa due to chronic deprivation of the epididymides of adequate testosterone.…”

Spermatozoa Epididymal Maturation in the Mexican Big-Eared Bat (Corynorhinus Mexicanus)

“…Although it has been recently shown that estrogens may be functionally indispensable for epididymal function [McCarthy et al 2006], it is known that epididymal functions in the majority of mammals, including epididymal sperm transport, sperm maturation and sperm storage, heavily depend on testicular androgen secretion [Holland et al 1992;Orgebin-Crist 1996;Moore and Akhondi 1996]. When, in otherwise intact animals, the cauda epididymis is physiologically isolated in situ by ligation of both of its extremes, the stored spermatozoa degenerate within several weeks but do not decrease noticeably in number [Lubicz-Nawrocki 1976;Jones 2004]. However, when subject to bilateral orchidectomy at the same time that the cauda epididymis is isolated, spermatozoa rapidly die and practically disappear (490%) in a few days.…”