Orchidectomy induces a wave of apoptotic cell death in the epididymis

Orchidectomy induces a wave of apoptotic cell death in the epididymis
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DOI:
10.1210/en.139.4.2128
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发表时间:
1998-04-01
期刊:
影响因子:
4.8
通讯作者:
Robaire, B
Robaire, B
中科院分区:
医学2区
文献类型:
--
作者:
Fan, XP;Robaire, B

文献摘要

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附睾是精子成熟和储存的场所。睾丸切除术后,该组织的重量减轻了 80%。在前列腺中,睾丸切除术导致的雄激素撤退与细胞凋亡相关。本研究的目的是调查睾丸切除术后大鼠附睾中发现的雄激素依赖性体重减轻是否涉及细胞凋亡。成年雄性Sprague-Dawley大鼠仅切除睾丸,通过原位TUNEL(TdT介导的dUTP-地高辛缺口末端标记)凋亡检测来鉴定凋亡细胞。睾丸切除后18小时,附睾起始段上皮细胞首先出现凋亡,第2天达到最大,睾丸切除后5天细胞凋亡消失。在附睾头中,24小时后首次发现细胞凋亡,第3天达到最大,直到第5天才可检测到。在附睾体中,细胞凋亡在第4天首次出现,在第5天达到峰值,到睾丸切除后第6天检测不到。在附睾尾部,细胞凋亡在第5天首次出现,在第6天达到峰值,并且偶尔在第7天检测到。在整个大鼠附睾中,凋亡细胞死亡特异性地局限于主细胞。通过使用琼脂糖凝胶电泳观察核小体大小的DNA片段化阶梯,证实了细胞凋亡的存在。睾丸切除术后的雄激素替代疗法表明,头、附睾体和附睾尾的细胞凋亡具有雄激素依赖性。然而,单独的雄激素不能完全阻止附睾起始段的细胞凋亡。传出管结扎在附睾起始段诱导的细胞凋亡模式与睾丸切除后相似,但附睾头的凋亡细胞较少,附睾体和附睾尾部没有凋亡细胞死亡。我们得出的结论是,通过睾丸切除术去除雄激素会引起附睾细胞凋亡。我们假设初始节段的细胞凋亡主要是由雄激素的撤退以及来自睾丸的管腔成分引起的。
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 mere 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 clay 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.