Orchidectomy Induces a Wave of Apoptotic Cell Death in the Epididymis*

Abstract

The epididymis is the site where spermatozoa are matured and stored. After orchidectomy, this tissue loses up to 80% of its weight. In the prostate, androgen withdrawal by orchidectomy is associated with apoptotic cell death. The objective of the present study was to investigate whether apoptotic cell death is involved in the androgen-dependent weight loss found in the rat epididymis after orchidectomy. Adult male Sprague-Dawley rats were orchidectomized, and apoptotic cells were identified by in situ TUNEL (TdT-mediated dUTP-digoxigenin nick end-labeling) apoptosis detection. Apoptosis first appeared in the epithelium of the initial segment of the epididymis 18 h after orchidectomy, reached a maximum on day 2, and disappeared by day 5 postorchidectomy. In the caput epididymidis, apoptosis was first found after 24 h, reached a maximum by day 3, and was detectable until day 5. In the corpus epididymidis, apoptosis was first seen on day 4, peaked on day 5, and was undetectable by day 6 postorchidectomy. In the cauda epididymidis, apoptosis was first seen on day 5, peaked on day 6, and was occasionally detected on day 7. Throughout the rat epididymis, apoptotic cell death was localized specifically to principal cells. The presence of apoptosis was confirmed with the observation of a ladder of nucleosomal sized DNA fragmentation by using agarose gel electrophoresis. Androgen replacement therapy after orchidectomy demonstrated that apoptosis in the caput, corpus, and cauda epididymidis was androgen dependent. However, androgens alone could not completely prevent apoptosis in the initial segment of the epididymis. Efferent duct ligation induced a similar pattern of apoptosis in the initial segment of the epididymis as that seen after orchidectomy, but there were fewer apoptotic cells in the caput epididymidis, and no apoptotic cell death in the corpus and cauda epididymidis. We conclude that withdrawal of androgen by orchidectomy induces a wave of apoptotic cell death in the epididymis; we hypothesize that apoptosis in the initial segment is caused primarily by withdrawal of androgen as well as by luminal components coming from the testis.

Photoperiod‐induced apoptosis in the male genital tract epithelia of the golden hamster

“…The values for the apoptotic indices were certainly low when compared with the situation after castration (M. Jara, R. Carballada & P. Esponda, unpublished results). Nevertheless, in castrated animals, the apoptotic index rises in the first few days after castration, but then, after a week show a striking decrease (Fan & Robaire, 1998). In our experimental model the indices are maintained or increased for weeks, so the total number of cells eliminated by apoptosis must be considerable.…”

“…Moreover, cell survival in the male tract is controlled by androgens and when their levels are experimentally reduced by orchidectomy, an apoptosis wave is induced in the epididymis and most accessory sex glands (Banerjee et al. , 1995; Fan & Robaire, 1998; Tsuji et al. , 1998).…”

Reduced levels of stromal sex hormone-binding globulin and androgen receptor dysfunction in the sperm storage region of the rat epididymis

“…Since in the cauda epididymidis the concentration of SHBG in the luminal fluid is low (Robaire & Hamzeh 2011), the androgenic supply is probably provided by the blood. This is confirmed by the fact that structural changes are not observed in the cauda epididymidis following the blockage of the androgenic supply from testicular fluid by efferent duct ligation (Fan & Robaire 1998). However, after testosterone withdrawal following orchiectomy, the cauda epididymidis undergoes severe structural changes, which are reversed after restoration of serum testosterone levels (Ezer & Robaire 2002).…”

“…It is known that DHT in the epididymis regulates the expression of genes associated with cell survival, proliferation and growth (Robaire & Hamzeh 2011). Under androgen withdrawal, all segments of the epididymis undergo apoptosis, leading to a reduction in duct diameter (Fan & Robaire 1998, Kempinas & Klinefelter 2014. In the present study, the high apoptotic index induced by cimetidine was coincident with the reduction of epididymal duct diameter.…”

Effects of 3-beta-diol, an androgen metabolite with intrinsic estrogen-like effects, in modulating the aquaporin-9 expression in the rat efferent ductules

“…Starting on the day of bilateral surgical castration, the rats were subjected to hormonal replacement, using subcutaneous injections once per day for 6 days. The treatment period was chosen considering that at this time both circulating and luminal source of hormones as well as sperm passing through the male tract has already been depleted [ 34 - 36 ]. Rats were randomly assigned to one of the following treatment groups (n = 5 for each group): 5 mg of 5α-dihydrotestosterone (DHT – Sigma, St.Louis, USA); 400 μg of 17-β-estradiol-3-benzoate (E2 – Sigma, St.Louis, USA); 3 mg of 5α-androstane-3β-17β-diol (3β-diol – Sigma, St.Louis, USA).…”