在缺乏睾丸-附睾卢米肾上腺素信号传导的小鼠体内,硫胺素可复制附睾初段的特征。

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2024-04-04 Epub Date: 2024-02-09 DOI:10.1262/jrd.2023-102
Daiji Kiyozumi
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引用次数: 0

摘要

哺乳动物附睾的生理功能通常由睾丸调节。除了睾丸莱伊杜氏细胞分泌的性类固醇以内分泌方式作用于附睾外,还有一种非性类固醇信号途径,即腔内信号途径。该信号途径涉及穿越男性生殖道的睾丸曲细精管内生殖细胞分泌的配体蛋白,这些配体蛋白可诱导附睾上皮分化。这些发现促使人们探究影响睾丸生理机能的治疗是否会通过干扰睾丸与附睾之间的交流而破坏附睾的功能。硫丹是一种烷化剂,在生殖生物学中常用于消耗睾丸的生殖细胞,但由于其对附睾的影响而未被充分研究。本研究采用组织学和转录组学分析方法,研究了服用硫丹对近端附睾的影响。值得注意的是,与载体二甲基亚砜(DMSO)相比,硫丹改变了附睾起始段的形态,导致管腔上皮细胞高度降低。与服用二甲基亚砜的小鼠相比,RNA测序在服用硫丹的小鼠附睾近端发现了185个明显下调的基因。比较转录组分析表明,服用硫丹的小鼠附睾转录组与传出导管连接的W/Wv和Nell2/-小鼠等体液素缺陷小鼠的转录组相似。然而,这与双侧睾丸切除小鼠的情况不同,后者的内分泌和腔内分泌信号通路同时被切断。总之,这些结果表明,硫丹对近端附睾的有害影响是消减睾丸-附睾腔内信号传导的次要后果。
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Busulfan administration replicated the characteristics of the epididymal initial segment observed in mice lacking testis-epididymis lumicrine signaling.

The physiological functions of the mammalian epididymis are typically regulated by the testes. In addition to sex steroids secreted by testicular Leydig cells, which act on the epididymis in an endocrine manner, there is a non-sex-steroidal signaling pathway known as the lumicrine pathway. This lumicrine signaling pathway involves ligand proteins secreted from germ cells within the testicular seminiferous tubules traversing the male reproductive tract, which induce epithelial differentiation in the epididymis. These findings prompted an inquiry into whether treatments influencing testis physiology can disrupt epididymal function by interfering with testis-epididymis communication. Busulfan, an alkylating agent commonly used to deplete testicular germ cells in reproductive biology, has not been sufficiently explored because of its effects on the epididymis. This study investigated the effects of busulfan administration on the proximal epididymis using histological and transcriptomic analyses. Notably, busulfan, as opposed to the vehicle dimethyl sulfoxide (DMSO), altered the morphology of the initial segment of the epididymis, leading to a reduction in the cell height of the luminal epithelium. RNA sequencing identified 185 significantly downregulated genes in the proximal epididymis of busulfan-administered mice compared to DMSO-administered mice. Comparative transcriptome analyses revealed similarities between the epididymal transcriptome of busulfan-administered mice and lumicrine-deficient mice, such as efferent-duct-ligated W/Wv and Nell2-/- mice. However, this differed from that of bilaterally orchidectomized mice, in which both the endocrine and lumicrine signaling pathways were simultaneously ablated. Collectively, these results suggested that the harmful effects of busulfan on the proximal epididymis are secondary consequences of the ablation of testis-epididymis lumicrine signaling.

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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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