Testicular degeneration in Huntington disease

Jeremy M. Van Raamsdonk; Zoe Murphy; David M. Selva; Reza Hamidizadeh; Jacqueline Pearson; Ǻsa Petersén; Maria Björkqvist; Cameron Muir; Ian R. Mackenzie; Geoffrey L. Hammond; A. Wayne Vogl; Michael R. Hayden; Blair R. Leavitt

Neurobiology of Disease (Jun 2007)

Testicular degeneration in Huntington disease

Jeremy M. Van Raamsdonk,
Zoe Murphy,
David M. Selva,
Reza Hamidizadeh,
Jacqueline Pearson,
Ǻsa Petersén,
Maria Björkqvist,
Cameron Muir,
Ian R. Mackenzie,
Geoffrey L. Hammond,
A. Wayne Vogl,
Michael R. Hayden,
Blair R. Leavitt

Affiliations

Jeremy M. Van Raamsdonk: Department of Medical Genetics and Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, 950 West 28th Ave., Vancouver, BC, Canada V5Z 4H4
Zoe Murphy: Department of Medical Genetics and Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, 950 West 28th Ave., Vancouver, BC, Canada V5Z 4H4
David M. Selva: Department of Obstetrics and Gynecology, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada
Reza Hamidizadeh: Department of Cellular and Physiological Science, University of British Columbia, Vancouver, BC, Canada
Jacqueline Pearson: Department of Medical Genetics and Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, 950 West 28th Ave., Vancouver, BC, Canada V5Z 4H4
Ǻsa Petersén: Department of Experimental Medical Sciences, Lund University, Lund, Sweden
Maria Björkqvist: Department of Experimental Medical Sciences, Lund University, Lund, Sweden
Cameron Muir: Department of Psychology, Centre for Neuroscience, Brock University, St. Catherines, Ontario, Canada
Ian R. Mackenzie: Department of Pathology, Vancouver General Hospital, Vancouver, BC, Canada
Geoffrey L. Hammond: Department of Obstetrics and Gynecology, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada
A. Wayne Vogl: Department of Cellular and Physiological Science, University of British Columbia, Vancouver, BC, Canada
Michael R. Hayden: Department of Medical Genetics and Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, 950 West 28th Ave., Vancouver, BC, Canada V5Z 4H4
Blair R. Leavitt: Department of Medical Genetics and Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, 950 West 28th Ave., Vancouver, BC, Canada V5Z 4H4; Corresponding author. Fax: +1 604 875 3840.

Journal volume & issue: Vol. 26, no. 3
pp. 512 – 520

Abstract

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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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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