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. 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. 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. 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.

中文翻译：

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蛋白质组学改变与肥胖小鼠精子畸胎症有关

肥胖症是危害人类健康的全球性危机。在这种情况下，精子质量下降的原因是精子浓度降低，活动力降低和精子畸形增加。这些改变的潜在机制在很大程度上仍然未知。这项研究确定了小鼠精子中与肥胖相关的蛋白质组学表达模式是否与从肥胖人类获得的精子中的蛋白表达模式平行。通过喂养高脂饮食（HFD）建立了肥胖小鼠模型。组织学分析确定了睾丸形态，计算机辅助精液分析仪（CASA）评估了精子参数。蛋白质组分析是使用无标记定量LC-MS / MS系统进行的。Western印迹，免疫组织化学和免疫荧光分析表征了睾丸，精子和临床样品中蛋白质的表达水平和定位。HFD引起的肝脂肪变性导致体重增加。精子活动力下降伴随着精子畸形的发展。差异蛋白质组学分析确定了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（CSPP1）和Centrin 1（CETN1）减少。在正常体重的小鼠中，CSPP1和CETN1均位于精母细胞和精子细胞中。它们的表达在精子后的平行于精子的manchette结构的微管轨迹的后区域中很明显，这影响了精子的头部成形和形态维持。此外，CSPP1定位在成熟精子的头尾耦合装置中，而CETN1的表达则被限定在精子头的顶峰后区域。重要的，与正常体重男性相比，超重和肥胖男性的精子CSPP1和CETN1丰度降低。这些发现表明，CETN1和CSPP1的区域不同表达和定位与精子发生和精子形态的维持密切相关。肥胖与小鼠和相关临床样品中CETN1和CSPP1丰度的下降以及精子形态的妥协有关。小鼠和人类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下降，包括畸形增加。肥胖与小鼠和相关临床样品中CETN1和CSPP1丰度的下降以及精子形态的妥协有关。小鼠和人类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下降，包括畸形增加。肥胖与小鼠和相关临床样品中CETN1和CSPP1丰度的下降以及精子形态的妥协有关。小鼠和人类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下降，包括畸形增加。