Testicular degeneration in Huntington disease
Testicular degeneration in Huntington disease
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DOI：
10.1016/j.nbd.2007.01.006
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发表时间：
2007-06
影响因子：
6.1
通讯作者：
J. V. Van Raamsdonk;Z. Murphy;D. Selva;R. Hamidizadeh;J. Pearson;Å. Petersén;M. Björkqvist;C. Muir;I. Mackenzie;G. Hammond;A. Vogl;M. Hayden;B. Leavitt
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文献类型：
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作者：
J. V. Van Raamsdonk;Z. Murphy;D. Selva;R. Hamidizadeh;J. Pearson;Å. Petersén;M. Björkqvist;C. Muir;I. Mackenzie;G. Hammond;A. Vogl;M. Hayden;B. Leavitt
亨廷顿病（HD）是一种成人发病的神经退行性疾病，其由HD基因中的CAG扩增引起。最近的工作已经证明了HD小鼠模型的睾丸变性和HD患者下丘脑-垂体-性腺（HPG）轴的改变。在这里，我们发现HD患者有特定的睾丸病理学，生殖细胞数量减少，曲细精管形态异常。在YAC 128小鼠模型中，睾丸变性在12个月大之前发生，但在12个月大时，没有证据表明睾丸激素水平降低或下丘脑中GnRH神经元丢失。这表明睾丸病理学是由突变亨廷顿蛋白在睾丸中的直接毒性作用引起的，并且亨廷顿蛋白在睾丸中受影响的细胞群中高度表达的事实支持了这一点。了解HD在睾丸中的发病机制可能会揭示导致大脑和睾丸变性的共同关键途径。
Huntington disease (HD) is an adult onset, neurodegenerative disorder that results from CAG expansion in the HD gene. Recent work has demonstrated testicular degeneration in mouse models of HD and alterations in the hypothalamic–pituitary–gonadal (HPG) axis in HD patients. Here, we show that HD patients have specific testicular pathology with reduced numbers of germ cells and abnormal seminiferous tubule morphology. In the YAC128 mouse model, testicular degeneration develops prior to 12 months of age, but at 12 months, there is no evidence for decreased testosterone levels or loss of GnRH neurons in the hypothalamus. This suggests that testicular pathology results from a direct toxic effect of mutant huntingtin in the testis and is supported by the fact that huntingtin is highly expressed in the affected cell populations in the testis. Understanding the pathogenesis of HD in the testis may reveal common critical pathways which lead to degeneration in both the brain and testis.