Influence of a leptin deficiency on testicular morphology, germ cell apoptosis, and expression levels of apoptosis-related genes in the mouse
Influence of a leptin deficiency on testicular morphology, germ cell apoptosis, and expression levels of apoptosis-related genes in the mouse
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DOI：
10.2164/jandrol.05133
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发表时间：
2006-03-01
影响因子：
--
通讯作者：
Mann, DR
中科院分区：
文献类型：
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作者：
Bhat, GK;Sea, TL;Mann, DR
瘦素缺乏(ob/ob)雄性小鼠是病态肥胖，表现出生殖功能受损。本研究的目的是评估瘦素缺乏对睾丸形态、生殖细胞发育、生殖细胞内的凋亡活性以及睾丸中凋亡相关基因表达水平的影响。将16周龄ob/ob雄性小鼠(n=8)和对照组(n=8)处死，称其生殖器官重量。睾丸进行组织形态分析(苏木精-伊红[H&E]染色)、生殖细胞凋亡检测(脱氧-UTP-地高辛缺口末端标记法)或凋亡相关基因表达分析(微阵列)。瘦素缺乏动物的睾丸横切面显示生精小管面积缩小，粗线期精母细胞减少，显示细长精子细胞/成熟精子的小管较少。某些ob/ob动物的睾丸内可见生殖细胞核凝聚和支持细胞空泡化。总体而言，ob/ob小鼠的生殖细胞，尤其是粗线期精母细胞中的凋亡活性增加。利用基因芯片技术，我们鉴定了9个促凋亡相关基因，它们在ob/ob小鼠的睾丸中的表达水平显著高于对照组。其中包括肿瘤坏死因子受体超家族1A和5(TNFR1和5)和肽聚糖识别蛋白(与外源性凋亡途径有关)，颗粒酶A和B，生长停滞和DNA损伤诱导的45伽马，鞘氨醇磷酸裂解酶1和半胱氨酸氨基转移酶9(与内在凋亡途径有关)。目前的研究结果表明，小鼠的瘦素缺乏与精子发生受损、生殖细胞凋亡增加以及睾丸内促凋亡基因的表达上调有关。
Leptin-deficient (ob/ob) male mice are morbidly obese and exhibit impaired reproductive function. The objective of this study was to assess the effect of a leptin deficiency on testicular morphology, germ cell development, apoptotic activity within germ cells, and expression levels of apoptosis-related genes in the testis. Sixteen week-old ob/ob male mice (n = 8) and controls (n = 8) were killed, and their reproductive organs were weighed. Testes were processed for either histomorphological analysis (hematoxylin and eosin [H&E] staining), germ cell apoptosis assessment (deoxy-UTP-digoxigenin nick end labeling [TUNEL] method), or apoptosis-related gene expression analysis (microarray). Cross sections of the testes of leptin-deficient animals showed reduced seminiferous tubule area, fewer pachytene spermatocytes, and fewer tubules exhibiting elongated spermatids/mature spermatozoa. Condensation of germ cell nuclei and Sertoli cell vacuolization were evident in the testes of some ob/ob animals. Overall there was an elevation of apoptotic activity in the germ cells of ob/ob mice, particularly within the pachytene spermatocytes. With microarray technology, we identified 9 proapoptosis-related genes that were expressed at a significantly higher level in the testes of ob/ob mice than in the testes of the controls. Among these were members of the tumor necrosis factor receptor super family 1A and 5 (TNFR1 and 5) and peptidoglycan recognition proteins (associated with the extrinsic apoptotic pathway), and granzymes A and B, growth arrest and DNA damage inducible 45 gamma, sphingosine phosphate lyase 1, and caspase 9 (associated with the intrinsic apoptotic pathway). The results of the current study show that a leptin deficiency in mice is associated with impaired spermatogenesis, increased germ cell apoptosis, and upregulated expression of proapoptotic genes within the testes.