Papalexi Eugenia, Persson Anna, Björkqvist Maria, Petersén Asa, Woodman Ben, Bates Gillian P, Sundler Frank, Mulder Hindrik, Brundin Patrik, Popovic Natalija
Neuronal Survival Unit, Department of Experimental Medical Science, Wallenberg Neuroscience Center, BMC A10, 221 84 Lund, Sweden.
Eur J Neurosci. 2005 Sep;22(6):1541-6. doi: 10.1111/j.1460-9568.2005.04324.x.
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.
据报道，亨廷顿舞蹈症（HD）患者的睾酮和促黄体生成素水平降低，性功能减退。在R6/2小鼠中也观察到了生殖器官萎缩和生育能力丧失，R6/2小鼠是目前研究最多的HD转基因模型。为了确定不育的原因，我们研究了性成熟期间R6/2雄性小鼠内侧隔区、布罗卡斜带和下丘脑促性腺激素释放激素（GnRH）的表达。我们发现，从5周龄开始，R6/2小鼠分析脑区中GnRH免疫反应性神经元数量逐渐减少，到9周龄时仅剩下10%的神经元，差异具有统计学意义。在12周龄的R6/2小鼠中检测到睾丸和精囊萎缩，同时血清和睾丸睾酮水平显著降低。这些结果表明，R6/2雄性小鼠不育要么是由于GnRH神经元死亡，要么是由于GnRH表达减少导致促性腺激素下游功能受损。促性腺激素替代疗法并不能减轻R6/2雄性小鼠的体重减轻或恢复其运动功能。
