Abdominal Temperature Induces Region-Specific p53-Independent Apoptosis in the Cauda Epididymidis of the Mouse1

Abstract

It is widely accepted that temperature regulates gene expression and function in the epididymis. However, the significance of reduced temperature of the scrotum in cell survival had not often been examined. Our hypothesis was that the experimental increase of the temperature could induce apoptosis. Using a surgical method that consists of surgically reflecting the cauda epididymidis in the abdomen, we have been able to show that this is the case. Apoptosis was examined by histologic procedures and by visualization of DNA fragmentation in agarose gels. We determined that the apoptosis is region-specific and affects only the principal cells of the proximal region of the cauda. It starts 12 h after surgery and ends by the third day. The apoptotic cells are eliminated by extrusion into the lumen and phagocytosis by adjacent cells. The complete molecular mechanism of apoptosis in this case remains unknown, but we have used the techniques of immunocytochemistry, Western blot, and reverse transcription-polymerase chain reaction to determine the role of some molecules. We have seen no significant role of androgens, the tumor suppressor p53, nor two heat shock proteins, hsp-25 and hsp-70. Nevertheless, we have detected a strong induction of bax and bcl-2 gene products. While the former should be responsible for the apoptosis observed, the latter would promote the survival of most of the cells of the cauda epididymis.

The Region-Specific Functions of Two Ubiquitin C-Terminal Hydrolase Isozymes along the Epididymis

“…The role of p53 in mediating apoptosis in the male genital tract has been demonstrated in several mice lines [28,29,42]. However, p53-independent apoptosis is suggested in the prostate and seminal vesicles by androgen withdrawal or in the rat epididymis by deprivation of luminal factors [3,11,14,38]. Previous studies indicated that Bcl-2 family proteins are involved in the induction or prevention of apoptosis [12,33,39,40].…”

Why are epididymal tumours so rare?

“…73 Such low apoptosis may reflect the presence of anti-apoptotic B-cell lymphoma-2 (Bcl-2) and absence of pro-apoptotic Fas. 74 The normal mouse epididymis expresses p53 and the apoptosis effector caspase 3, 75 yet apoptosis in this organ following cryptepididymis and castration is independent of p53 and Fas/FasL, 75,76 as is rat epididymal apoptosis after efferent duct ligation. 73 Senescence Another mechanism of intrinsic tumour suppression is age-independent 'senescence', a signal transduction programme leading to irreversible arrest of cell proliferation, accompanied by distinct changes in cellular phenotype.…”

Ectopic testis in coati (Nasua nasua Linnaeus, 1766)

“…Furthermore, spermatozoa were not observed in the epididymal lumen. Several factors may contribute to the pathology observed in the ectopic epididymis in this study, including exposure to a higher temperature as reported by Jara et al (2002).…”