Retarded differentiation of Leydig cells and increased apoptosis of germ cells in the initial round of spermatogenesis of rats with lethal dwarf and epilepsy (lde/lde) phenotypes.
Retarded differentiation of Leydig cells and increased apoptosis of germ cells in the initial round of spermatogenesis of rats with lethal dwarf and epilepsy (lde/lde) phenotypes.
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在具有致死性侏儒症和癫痫（lde/lde）表型的大鼠的第一轮精子发生中，Leydig 细胞分化延迟，生殖细胞凋亡增加。
DOI：
10.2164/jandrol.108.005066
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发表时间：
2008
影响因子：
--
通讯作者：
Hiroetsu Suzuki
中科院分区：
文献类型：
--
作者：
M. Takenaka;M. Yagi;K. Amakasu;Katsushi Suzuki;Hiroetsu Suzuki
lde/lde大鼠表现出严重的侏儒表型，具有产后早期致死率和癫痫发作的高发生率。该模型在 16 至 63 天龄之间首次检测到癫痫发作，大多以狂奔开始，然后发展为全身强直阵挛性惊厥。由于我们的组织学检查在28日龄时发现这些动物的海马和杏仁体中存在许多细胞外空泡，因此这些病理改变可能与lde/lde大鼠的癫痫发生有关。除了这些缺陷之外，与野生型对照相比，雄性 lde/lde 大鼠的睾丸明显较小，生殖细胞数量减少，成年型 Leydig 细胞成熟度较差。在本研究中，我们进行了解剖学、组织学和内分泌学检查，以表征 21、28、35 和 56 天龄的 lde/lde 大鼠的睾丸表型。雄性lde/lde大鼠的睾丸和副性器官生长严重迟缓。与对照组相比，在所有检查时间点，他们的生精小管明显更小，并且含有明显更少的生殖细胞。在lde/lde大鼠的睾丸中观察到，21日龄和28日龄时支持细胞显着减少，28日龄时精母细胞数量显着减少，56日龄时精子细胞出现延迟。在lde/lde生精小管中检测到更多TUNEL（T&T介导的duTP-生物素缺口末端标记）阳性细胞，并且在28日龄时记录到最大数量的凋亡细胞。在 lde/lde 大鼠的睾丸中，3β-羟基类固醇脱氢酶阳性成年型 Leydig 细胞和 11β-羟基类固醇脱氢酶阳性成熟成年型 Leydig 细胞的增加也严重迟缓。与这些缺陷相一致的是，在 28 日龄时，在 lde/lde 雄性中检测到血浆卵泡刺激素 (FSH)、黄体生成素 (LH) 和睾酮浓度显着降低，并且在 lde/lde 雄性垂体前叶中检测到 FSH 免疫染色较弱，LH 阳性细胞的细胞质较小。尽管 35 日龄后血浆 LH 水平正常，但在 56 日龄时检测到血浆睾酮水平显着降低。这些结果表明正常的 lde 等位基因与青春期前促性腺激素的升高和成人型 Leydig 细胞的正常发育有关。由于lde/lde大鼠在下丘脑-垂体-睾丸轴建立期间经历癫痫发作，因此lde/lde大鼠可用作小儿癫痫生殖障碍的模型。
The lde/lde rats show a severe dwarf phenotype with early postnatal lethality and a high incidence of epileptic seizure. Seizures are first detected in this model between 16 and 63 days of age, and mostly begin as wild running and progress to generalized tonic-clonic convulsions. Because our histological examination detected many extracellular vacuoles in the hippocampus and amygdaloid bodies of these animals at 28 days of age, these pathological alterations may be related to the epileptogenesis in lde/lde rats. In addition to these defects, male lde/lde rats have apparently smaller testes with reduced number of germ cells and poorly matured adult-type Leydig cells in comparison with wild-type controls. In the present study, we performed anatomical, histological, and endocrinologic examinations to characterize the testicular phenotype of lde/lde rats at 21, 28, 35, and 56 days of age. Male lde/lde rats showed severely retarded growth of the testes and accessory sex organs. Their seminiferous tubules were significantly smaller and contained markedly fewer germ cells at all time points examined as compared with controls. Significantly fewer Sertoli cells at 21 and 28 days of age, markedly decreased spermatocyte number at 28 days of age, and delayed appearance of spermatids at 56 days of age were observed in the testes of lde/lde rats. More TUNEL (T&T-mediated duTP-biotin nick-end labeling)-positive cells were detected in lde/lde seminiferous tubules, and the largest number of apoptotic cells was recorded at 28 days of age. The increases in 3beta-hydroxysteroid dehydrogenase-positive adult-type Leydig cells and 11beta-hydroxysteroid dehydrogenase-positive mature adult-type Leydig cells were also severely retarded in the testes of lde/lde rats. Consistent with these defects, significantly lower plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone concentrations were detected in lde/lde males at 28 days of age, and weak immunostaining for FSH and smaller cytoplasm of LH-positive cells were detected in the anterior pituitary lobes of lde/lde males. Despite a normal level of plasma LH after 35 days of age, a significantly lower level of plasma testosterone was detected at 56 days of age. These results indicate that the normal lde allele is related to prepubertal elevations of gonadotropins and normal development of adult-type Leydig cells. Because lde/lde rats experience epileptic seizures during the period when the hypothalamus-pituitary-testicular axis is established, lde/lde rats would be useful as a model for reproductive disorder with pediatric epilepsy.
DOI：
10.1073/pnas.0404743101
发表时间：
2004-12-07
影响因子：
11.1
作者：
Ma, XP;Dong, YL;Kumar, TR
通讯作者：
Kumar, TR