Testicular degeneration in Huntington disease

被引：75
作者：
Van Raamsdonk, Jeremy M.
Murphy, Zoe
Selva, David M.
Hamidizadeh, Reza
Pearson, Jacqueline
Petersen, Asa
Bjorkqvist, Maria
Muir, Cameron
Mackenzie, Ian R.
Hammond, Geoffrey L.
Vogl, A. Wayne
Hayden, Michael R.
Leavitt, Blair R.
机构：
[1] Univ British Columbia, Child & Family Res Inst, Dept Med Genet, Vancouver, BC V5Z 4H4, Canada
[2] Univ British Columbia, Child & Family Res Inst, Dept Obstet & Gynecol, Vancouver, BC, Canada
[3] Univ British Columbia, Dept Cellular & Physiol Sci, Vancouver, BC, Canada
[4] Lund Univ, Dept Expt Med Sci, Lund, Sweden
[5] Brock Univ, Ctr Neurosci, Dept Psychol, St Catharines, ON, Canada
[6] Vancouver Gen Hosp, Dept Pathol, Vancouver, BC, Canada
来源：
NEUROBIOLOGY OF DISEASE | 2007年 / 26卷 / 03期
基金：
加拿大健康研究院;
关键词：
Huntington disease; Huntingtin; testis; hypothalamic-pituitary-gonadal; axis; testosterone; YAC128 mouse model; testicular degeneration;
D O I：
10.1016/j.nbd.2007.01.006
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
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. (c) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码：512 / 520
页数：9
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