Liang Chen, Chen Mingyang, Mu Zhidan, Tian Xinyan, Zhao Wenzhen, Hu Yarong, Su Juan
Department of Physiology and Pathophysiology, School of Basic Medicine, Dali University, Dali, 671003, China.
Department of Histology and Embryology, School of Basic Medicine, Dali University, Dali, 671003, China.
Biol Trace Elem Res. 2025 Jan 16. doi: 10.1007/s12011-025-04512-5.
The aim of this study was to explore the role of the ZnT9 protein in obesity-induced sperm maturation disorders in men. We generated a mouse model of obesity-induced weak spermatogenesis via a high-fat diet (HFD) for 10 weeks. In addition to the HFD, a 5-week intervention of salubrinal (SAL) (an inhibitor of endoplasmic reticulum stress) (1 mg/kg/day), ZnSO (15 mg/kg/day), and their combination was started at week 6, after which sperm viability and epididymal tissue damage were assessed. To investigate the role of the ZnT9 protein in spermatogenesis, the expression levels of the ZnT9 protein, endoplasmic reticulum stress (ERS)-related protein, Wnt pathway protein, and apoptosis-related protein in epididymal tissue were measured. Compared with those in the normal (N) group, the mice in the HFD group presented decreased sperm motility, damaged epididymal tissue, epididymal tissue showed decreased expression of ZnT9, β-catenin, LEF protein and mRNA, and increased expression of total cholesterol (TC) and triglycerides (TG), GRP78, Caspase-3, BAX protein and mRNA, as well as increased apoptosis as shown by TUNEL staining. Compared with the HFD group, HFD + ZnSO group, HFD + SAL group, and HFD + ZnSO + SAL groups resulted in reduced epididymal damage, improved decreased total cholesterol (TC) and triglycerides (TG), sperm viability, increased expression of ZnT9, β-catenin, LEF protein and mRNA, and decreased expression of GRP78, Caspase-3, and BAX protein and mRNA, as well as decreased apoptosis as shown by TUNEL staining in epididymal tissues. According to this study, obesity leads to elevated ERS and affects ZnT9 protein synthesis. Inhibition of the Wnt pathway ultimately leads to cell death and damage in epididymal tissue and decreased sperm viability.
本研究的目的是探讨锌转运体9（ZnT9）蛋白在男性肥胖诱导的精子成熟障碍中的作用。我们通过高脂饮食（HFD）10周建立了肥胖诱导的精子发生减弱的小鼠模型。除高脂饮食外，在第6周开始对盐芦比诺（SAL）（一种内质网应激抑制剂）（1毫克/千克/天）、硫酸锌（15毫克/千克/天）及其组合进行为期5周的干预，之后评估精子活力和附睾组织损伤情况。为了研究ZnT9蛋白在精子发生中的作用，检测了附睾组织中ZnT9蛋白、内质网应激（ERS）相关蛋白、Wnt信号通路蛋白和凋亡相关蛋白的表达水平。与正常（N）组相比，高脂饮食组小鼠精子活力下降，附睾组织受损，附睾组织中ZnT9、β-连环蛋白、淋巴样增强因子（LEF）蛋白和mRNA表达降低，总胆固醇（TC）和甘油三酯（TG）、葡萄糖调节蛋白78（GRP78）、半胱天冬酶-3（Caspase-3）、凋亡相关蛋白BAX蛋白和mRNA表达增加，TUNEL染色显示凋亡增加。与高脂饮食组相比，高脂饮食+硫酸锌组、高脂饮食+盐芦比诺组和高脂饮食+硫酸锌+盐芦比诺组附睾损伤减轻，总胆固醇（TC）和甘油三酯（TG）降低、精子活力改善，ZnT9、β-连环蛋白、LEF蛋白和mRNA表达增加，GRP78、Caspase-3和BAX蛋白及mRNA表达降低，附睾组织TUNEL染色显示凋亡减少。根据本研究，肥胖导致内质网应激升高并影响ZnT9蛋白合成。Wnt信号通路的抑制最终导致附睾组织细胞死亡和损伤以及精子活力下降。
