New Players in the Infertility of a Mouse Model of Lysosomal Storage Disease: The Hypothalamus-Pituitary-Gonadal Axis
New Players in the Infertility of a Mouse Model of Lysosomal Storage Disease: The Hypothalamus-Pituitary-Gonadal Axis
复制标题
溶酶体贮积病小鼠不育模型的新参与者：下丘脑-垂体-性腺轴
作者：
P. Piomboni;L. Governini;Martina Gori;Erica Puggioni;E. Costantino‐Ceccarini;A. Luddi
哺乳动物精子发生是一个复杂的激素依赖性发育过程，其中不同细胞类型之间的相互作用受到精细调节。任何精子成熟步骤受到干扰的小鼠模型为精子发生的分子控制提供了重要的见解。Twitcher小鼠是Krabbe病的模型，其特征是半乳糖神经酰胺酶（GALC）缺乏，GALC是一种溶酶体酶，可水解半乳糖神经酰胺的末端半乳糖，半乳糖神经酰胺是髓鞘膜的典型成分。此外，GALC还能催化半乳糖基-烷基-酰基-甘油水解末端半乳糖，半乳糖基-烷基-酰基-甘油是半脂质的前体，在生殖细胞膜上特异性表达。本课题组先前报道的数据表明，糖脂在精子成熟和分化中起重要作用。此外，我们假设影响Twitcher小鼠的中枢神经系统的严重损伤可能会干扰下丘脑-垂体-性腺轴功能，从而导致不育。为了强调这一假设，我们在分子水平上确定了参与精子发生调节的脑激素表达模式的潜在变化。
Mammalian spermatogenesis is a complex hormone-dependent developmental program where interactions between different cell types are finely regulated. Mouse models in which any of the sperm maturation steps are perturbed provide major insights into the molecular control of spermatogenesis. The Twitcher mouse is a model for the Krabbe disease, characterized by the deficiency of galactosylceramidase (GALC), a lysosomal enzyme that hydrolyzes the terminal galactose from galactosylceramide, a typical component of the myelin membrane. In addition, GALC catalyzes the hydrolysis of the terminal galactose from galactosyl-alkyl-acyl-glycerol, precursor of seminolipids, specifically expressed on the membrane of germ cells. Previous data reported by our group demonstrated that glycolipids play an important role in sperm maturation and differentiation. Moreover, we hypothesized that the severe impairment of the central nervous system that affects the Twitcher mouse could interfere with the hypothalamus-pituitary-gonadal axis function, contributing to infertility. To highlight this hypothesis we have determined, at molecular level, the potential variation in expression pattern of brain hormones involved in spermatogenesis regulation.
影响因子：
6
作者：
Butler, A;He, XX;Schuchman, EH
通讯作者：
Schuchman, EH
影响因子：
4.5
作者：
Michaelis, M.;Langhammer, M.;Weitzel, J. M.
通讯作者：
Weitzel, J. M.
影响因子：
4.8
作者：
H. Nitta;D. Bunick;R. Hess;L. Janulis;S. Newton;C. Millette;Y. Osawa;Y. Shizuta;K. Toda;J. Bahr
通讯作者：
H. Nitta;D. Bunick;R. Hess;L. Janulis;S. Newton;C. Millette;Y. Osawa;Y. Shizuta;K. Toda;J. Bahr