Kotula-Balak Małgorzata, Lenartowicz Małgorzata, Kowal Małgorzata, Styrna Józefa, Bilińska Barbara
Department of Endocrinology and Tissue Culture, Institute of Zoology, Jagiellonian University, Ingardena 6, 30-060 Krakow, Poland.
Theriogenology. 2007 Jan 15;67(2):423-34. doi: 10.1016/j.theriogenology.2006.08.016. Epub 2006 Oct 11.
The aim of this study was to determine whether testicular cells of mice with the mosaic mutation, associated with abnormal copper metabolism, are able to aromatize androgens to estrogens, and what is the putative role of estrogens in the gonad of the mutant male. Mosaic is a lethal mutation; affected males usually die on about day 16. Those, which survive to reach sexual maturity, are valuable research subjects. In testes of young and adult mutants, histological analysis revealed the presence of many degenerating seminiferous tubules besides normal-looking ones. Additionally, high numbers of apoptotic germ cells were observed, especially in young mutants when compared with the controls. Positive immunostaining for aromatase was found in cultured Leydig cells and testicular sections of both control and mutant males. The intensity of immunostaining was always stronger in the mosaic mice. In both groups, Western-blot analysis revealed the presence of aromatase protein as a single band of approximately 55 kDa. In the mosaic males, levels of testosterone in cultured Leydig cells, whole testes, and in blood plasma were lower than in those of the respective controls. On the contrary, estradiol concentrations were always higher in the mutants. Both in vivo and in vitro studies indicate that morphological and functional changes in the testes of the mosaic mice mainly result from defective copper metabolism. The higher level of endogenous estrogens can additionally enhance morphological alterations within the testes. It seems also likely that excess estrogens may affect the survival rate of the mosaic males.
本研究的目的是确定与铜代谢异常相关的嵌合突变小鼠的睾丸细胞是否能够将雄激素芳香化为雌激素，以及雌激素在突变雄性性腺中的假定作用。嵌合是一种致死突变；受影响的雄性通常在大约第16天死亡。那些存活到性成熟的个体是有价值的研究对象。在幼年和成年突变体的睾丸中，组织学分析显示，除了外观正常的生精小管外，还存在许多退化的生精小管。此外，观察到大量凋亡的生殖细胞，尤其是与对照组相比，幼年突变体中的凋亡生殖细胞更多。在对照和突变雄性的培养睾丸间质细胞和睾丸切片中均发现芳香化酶的阳性免疫染色。嵌合小鼠的免疫染色强度总是更强。在两组中，蛋白质印迹分析均显示芳香化酶蛋白以一条约55 kDa的单带形式存在。在嵌合雄性中，培养的睾丸间质细胞、整个睾丸和血浆中的睾酮水平均低于各自的对照组。相反，突变体中的雌二醇浓度总是更高。体内和体外研究均表明，嵌合小鼠睾丸的形态和功能变化主要是由铜代谢缺陷引起的。内源性雌激素水平升高还可额外加剧睾丸内的形态学改变。过量雌激素似乎也可能影响嵌合雄性的存活率。
