ORCHIECTOMY INDUCES A WAVE OF APOPTOTIC CELL-DEATH IN THE EPIDIDYMIS

The epididymis is the site where spermatozoa are matured and stored. A fter orchidectomy, this tissue loses up to 80% of its weight. In the p rostate, androgen withdrawal by orchidectomy is associated with apopto tic cell death. The objective of the present study was to investigate whether apoptotic cell death is involved in the androgen-dependent wei ght loss found in the rat epididymis after orchidectomy. Adult male Sp rague-Dawley rats mere orchidectomized, and apoptotic cells were ident ified by in situ TUNEL (TdT-mediated dUTP-digoxigenin nick end-labelin g) 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 clay 5 postorchidectomy. In ti le caput epididymidis, apoptosis was first found after 24 h, reached a maximum by day 3, and was detectable until day 5. In the corpus epidi dymidis, apoptosis was first seen on day 4, peaked on day 5, and was u ndetectable by day 6 postorchidectomy. In the cauda epididymidis, apop tosis was first seen on day 5, peaked on day 6, and was occasionally d etected on day 7. Throughout the rat epididymis, apoptotic cell death was localized specifically to principal cells. The presence of apoptos is was confirmed with the observation of a ladder of nucleosomal sized DNA fragmentation by using agarose gel electrophoresis. Androgen repl acement 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 p attern of apoptosis in the initial segment of the epididymis as that s een after orchidectomy, but there were fewer apoptotic cells in the ca put 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 hypothesi ze that apoptosis in the initial segment is caused primarily by withdr awal of androgen as well as by luminal components coming from the test is.