Proteomic alterations underlie an association with teratozoospermia in obese mice sperm
Proteomic alterations underlie an association with teratozoospermia in obese mice sperm
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蛋白质组学改变与肥胖小鼠精子畸形精子症相关
DOI：
10.1186/s12958-019-0530-7
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发表时间：
2019-10-24
影响因子：
4.4
通讯作者：
Ding, Zhide
中科院分区：
文献类型：
--
作者：
Peng, Yuanhong;Zhao, Wenzhen;Ding, Zhide
肥胖是危害人类健康的世界性危机。在这种情况下，精子质量的下降源于精子浓度、活力的降低和精子畸形的增加。这些改变的机制在很大程度上仍然未知。本研究旨在确定小鼠精子中与肥胖相关的蛋白质组表达模式是否与肥胖人类精子中的表达模式相似。方法采用高脂饲料喂养建立肥胖小鼠模型。组织学分析确定了睾丸形态，计算机辅助精液分析仪（CASA）评价了精子参数。使用无标记的定量LC-MS/MS系统进行蛋白质组分析。蛋白质印迹，免疫组织化学和免疫荧光分析的特点蛋白质表达水平和定位在睾丸，精子和临床样本。结果HFD组大鼠体重增加，肝脂肪变性。精子活力下降伴随精子畸形的发展。差异蛋白质组学分析发现，肥胖小鼠精子中的细胞骨架蛋白，中心体和纺锤体极相关蛋白1（CSPP 1）和中心蛋白1（CETN 1）减少。在正常体重小鼠中，CSPP 1和CETN 1均定位于精母细胞和精子细胞中。它们的表达是可观的顶体后区平行的微管轨道的鞍状结构的精子细胞，影响精子细胞头部的形状和形态的维持。此外，CSPP 1定位于成熟精子的头-尾耦合器，而CETN 1的表达被限定在精子头部内的顶体后区域。重要的是，与正常体重的男性相比，超重和肥胖男性的精子CSPP 1和CETN 1丰度都有所下降。结论CETN 1和CSPP 1的区域性表达和定位与精子发生和精子形态维持密切相关。肥胖与小鼠和相关临床样品中CETN 1和CSPP 1丰度的下降以及精子形态的损害有关。小鼠和人类中蛋白质表达改变之间的这种平行性表明，这些影响可能导致精子质量差，包括畸形增加。
Background Obesity is a worldwide crisis impairing human health. In this condition, declines in sperm quality stem from reductions in sperm concentration, motility and increase in sperm deformity. The mechanism underlying these alterations remains largely unknown. This study, determined if obesity-associated proteomic expression patterns in mice sperm parallel those in spermatozoa obtained from obese humans. Methods An obese mouse model was established via feeding a high-fat diet (HFD). Histological analysis identified testicular morphology and a computer assisted semen analyzer (CASA) evaluated sperm parameters. Proteome analysis was performed using a label-free quantitative LC-MS/MS system. Western blot, immunohistochemical and immunofluorescent analyses characterized protein expression levels and localization in testis, sperm and clinical samples. Results Bodyweight gains on the HFD induced hepatic steatosis. Declines in sperm motility accompanied sperm deformity development. Differential proteomic analysis identified reduced cytoskeletal proteins, centrosome and spindle pole associated protein 1 (CSPP1) and Centrin 1 (CETN1), in sperm from obese mice. In normal weight mice, both CSPP1 and CETN1 were localized in the spermatocytes and spermatids. Their expression was appreciable in the post-acrosomal region parallel to the microtubule tracks of the manchette structure in spermatids, which affects spermatid head shaping and morphological maintenance. Moreover, CSPP1 was localized in the head-tail coupling apparatus of the mature sperm, while CETN1 expression was delimited to the post-acrosomal region within the sperm head. Importantly, sperm CSPP1 and CETN1 abundance in both the overweight and obese males decreased in comparison with that in normal weight men. Conclusion These findings show that regionally distinct expression and localization of CETN1 and CSPP1 is strongly related to spermiogenesis and sperm morphology maintaining. Obesity is associated with declines in the CETN1 and CSPP1 abundance and compromise of both sperm morphology in mice and relevant clinical samples. This parallelism between altered protein expression in mice and humans suggests that these effects may contribute to poor sperm quality including increased deformity.