Testicular degeneration in Huntington disease

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

doi:10.1016/j.nbd.2007.01.006

Testicular degeneration in Huntington disease

Neurobiol Dis. 2007 Jun;26(3):512-20. doi: 10.1016/j.nbd.2007.01.006. Epub 2007 Jan 27.

Authors

Jeremy M Van Raamsdonk¹, Zoe Murphy, David M Selva, Reza Hamidizadeh, Jacqueline Pearson, Asa Petersén, Maria Björkqvist, Cameron Muir, Ian R Mackenzie, Geoffrey L Hammond, A Wayne Vogl, Michael R Hayden, Blair R Leavitt

Affiliation

¹ 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.

PMID: 17433700
DOI: 10.1016/j.nbd.2007.01.006

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Animals
Disease Models, Animal
Germ Cells / metabolism
Germ Cells / pathology
Gonadotropin-Releasing Hormone / metabolism
Humans
Huntingtin Protein
Huntington Disease / complications*
Huntington Disease / metabolism
Huntington Disease / physiopathology*
Hypothalamo-Hypophyseal System / metabolism
Hypothalamo-Hypophyseal System / physiopathology
Male
Mice
Mice, Transgenic
Middle Aged
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / metabolism*
Neurons / metabolism
Neurons / pathology
Nuclear Proteins / genetics
Nuclear Proteins / metabolism*
Seminiferous Tubules / metabolism
Seminiferous Tubules / pathology
Seminiferous Tubules / physiopathology
Testicular Diseases / etiology*
Testicular Diseases / metabolism
Testicular Diseases / physiopathology*
Testis / metabolism
Testis / pathology
Testis / physiopathology*
Testosterone / blood

Substances

HTT protein, human
Huntingtin Protein
Nerve Tissue Proteins
Nuclear Proteins
Gonadotropin-Releasing Hormone
Testosterone