Characterization of the role of tumor necrosis factor apoptosis inducing ligand (TRAIL) in spermatogenesis through the evaluation of trail gene-deficient mice.
Characterization of the role of tumor necrosis factor apoptosis inducing ligand (TRAIL) in spermatogenesis through the evaluation of trail gene-deficient mice.
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DOI：
10.1371/journal.pone.0093926
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Richburg JH
中科院分区：
文献类型：
--
作者：
Lin YC;Richburg JH
TRAIL(TNFSF10/Apo2L)是肿瘤坏死因子超家族蛋白的一员，在人和啮齿动物的睾丸中均有表达。尽管TRAIL在精子发生中的功能尚不清楚，但TRAIL被认为是通过与其同源受体DR4(TRAIL-R1/TNFRSF10A)和DR5(TRAIL-R2/TNFRSF10B)结合来诱导细胞凋亡。在这里，我们利用TRAIL基因缺陷(TRAIL−/−)小鼠，通过测量出生后28天(青春期)和PND56天(成年)的睾丸重量、生殖细胞凋亡和精子细胞数来评估TRAIL在精子发生中的作用。TRAIL−/−小鼠在两个年龄段与野生型C57BL/6J相比，睾丸与体重的比率显著降低。此外，TRAIL−/−小鼠(PND28)的基础生殖细胞凋亡指数(AI)(AI)显著高于C57BL/6J(3.5%)。成年C57BL/6J小鼠睾丸AI低于PND 28只C57BL/6J小鼠(2.2)。然而，在成年Trail−/−小鼠中，AI仍然高于对照组(9.0)；这表明生殖细胞凋亡率相对较高。切割caspase-8(Cc8)和切割caspase-9(Cc9)(分别代表外源性和内源性凋亡途径的标志物)的表达显示，在成年Trail−/−小鼠中，这两条途径的活性都是C57BL/6J小鼠的两倍。与C57BL/6J相比，成年TRAIL−/−小鼠的精子细胞数显著减少54%，表明这些动物的成熟精子产量显著下降。综上所述，这些发现表明TRAIL是维持睾丸生殖细胞稳态和精子发生功能的重要信号分子。
TRAIL (TNFSF10/Apo2L) is a member of the tumor necrosis factor (TNF) superfamily of proteins and is expressed in human and rodent testis. Although the functional role of TRAIL in spermatogenesis is not known, TRAIL is recognized to induce apoptosis via binding to its cognate receptors; DR4 (TRAIL-R1/TNFRSF10A) and DR5 (TRAIL-R2/TNFRSF10B). Here, we utilize Trail gene-deficient (Trail −/−) mice to evaluate the role of TRAIL in spermatogenesis by measuring testis weight, germ cell apoptosis, and spermatid head count at postnatal day (PND) 28 (pubertal) and PND 56 (adult). Trail−/− mice have significantly reduced testis to body weight ratios as compared to wild-type C57BL/6J at both ages. Also, Trail −/− mice (PND 28) show a dramatic increase in basal germ cell apoptotic index (AI, 16.77) as compared to C57BL/6J (3.5). In the testis of adult C57BL/6J mice, the AI was lower than in PND 28 C57BL/6J mice (2.2). However, in adult Trail −/− mice, the AI was still higher than that of controls (9.0); indicating a relative high incidence of germ cell apoptosis. Expression of cleaved caspase-8 (CC8) and cleaved caspase-9 (CC9) (markers of the extrinsic and intrinsic apoptotic pathway, respectively) revealed a two-fold increase in the activity of both pathways in adult Trail −/− mice compared to C57BL/6J. Spermatid head counts in adult Trail −/− mice were dramatically reduced by 54% compared to C57BL/6J, indicating these animals suffer a marked decline in the production of mature spermatozoa. Taken together, these findings indicate that TRAIL is an important signaling molecule for maintaining germ cell homeostasis and functional spermatogenesis in the testis.
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