Reduction of GnRH and infertility in the R6/2 mouse model of Huntington's disease.
Reductions in testosterone and luteinizing hormone levels and reduced sexual functions have been reported in Huntington's disease (HD) patients. Atrophy of the reproductive organs and loss of fertility have also been observed in the R6/2 mouse, which is currently the most studied transgenic model of HD. In an effort to define the cause of infertility we studied the expression of gonadotropin-releasing hormone (GnRH) in the medial septum, diagonal band of Broca and hypothalamus of R6/2 male mice during sexual maturation. We found a progressive reduction in the numbers of GnRH-immunoreactive neurons in the analysed brain areas of R6/2 mice starting at 5 weeks of age and becoming statistically significant with only 10% of the neurons remaining by 9 weeks of age. Atrophy of testes and seminal vesicles combined with a significant reduction in serum and testicular testosterone levels were detected in 12-week-old R6/2mice. These results suggest that infertility in the R6/2 males is due either to death of GnRH neurons or to a reduction in GnRH expression leading to a downstream impairment of the gonadotropic hormones. Gonadotropic hormone replacement did not mitigate weight loss or restore motor function in R6/2 males.
Papalexi
Eugenia
E
Neuronal Survival Unit, Department of Experimental Medical Science, Wallenberg Neuroscience Center, BMC A10, 221 84 Lund, Sweden.
Persson
Anna
A
Björkqvist
Maria
M
Petersén
Asa
A
Woodman
Ben
B
Bates
Gillian P
GP
Sundler
Frank
F
Mulder
Hindrik
H
Brundin
Patrik
P
Popovic
Natalija
N
D000465:Algorithms; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000235:genetics / Q000502:physiology; D004195:Disease Models, Animal; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D006816:Huntington Disease / Q000235:genetics* / Q000378:metabolism*; D007006:Hypogonadism / Q000235:genetics; D007150:Immunohistochemistry; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009929:Organ Size / Q000187:drug effects; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D013739:Testosterone / Q000097:blood / Q000494:pharmacology
D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone