Testicular degeneration in Huntington disease.
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.
Van Raamsdonk
Jeremy M
JM
Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, 950 West 28th Ave., Vancouver, BC, Canada V5Z 4H4.
Murphy
Zoe
Z
Selva
David M
DM
Hamidizadeh
Reza
R
Pearson
Jacqueline
J
Petersén
Asa
A
Björkqvist
Maria
M
Muir
Cameron
C
Mackenzie
Ian R
IR
Hammond
Geoffrey L
GL
Vogl
A Wayne
AW
Hayden
Michael R
MR
Leavitt
Blair R
BR
D000328:Adult; D000368:Aged; D000818:Animals; D004195:Disease Models, Animal; D005854:Germ Cells / Q000378:metabolism / Q000473:pathology; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012671:Seminiferous Tubules / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013733:Testicular Diseases / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D013737:Testis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D013739:Testosterone / Q000097:blood
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone