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Down regulating PHGDH affects the lactate production of sertoli cells in varicocele

作者:Wenbin Guo, Zhenhui Huang, Cheng Yang, Xian-yuan Lv, Hui Xia, Hu Tian, Jian-Kun Yang, Qi-Zhao Zhou, Mingkun Chen, Kangyi Xue, Cundong Liu · 发表于:Reproductive Biology and Endocrinology · 年份:2020 · DOI:10.1186/s12958-020-00625-9 · 被引用次数:17 · 研究领域:Sperm and Testicular Function、Reproductive Biology and Fertility、Endoplasmic Reticulum Stress and Disease

BACKGROUND: Although varicocele is considered to be one of the leading causes of male infertility, the precise mechanism underlying how varicocele leads to male infertility is not completely understood. We found the lactate concentration on the varicocele side of the patients was decreased compare with peripheral venous blood. In the testicles, the lactate produced by the sertoli cells through the glycolysis pathway provides most of the energy needed for spermatogenesis, the reduction of lactate will affect spermatogenesis. The objective of this study was to investigate the mechanism of this abnormal energy metabolism phenomenon in varicocele. METHODS: In this study, we collected the testicular tissue from patients with varicocele, the glycolysis related proteins PHGDH was identified by iTRAQ proteomics technology. Experimental rat varicocele model was constructed according to our new clip technique, the mRNA and protein expression levels of PHGDH were examined with qRT-PCR and Western blotting. We constructed a sertoli cell of PHGDH down-regulation model, and then detected the glucose consumption, LDH activities and lactate production in the sertoli cells. Western blot was conducted to investigate the effects of PHGDH on the expression of phosphoserine phosphatase (PSPH) and Pyruvate kinase M2 (PKM2). Flow cytometry was used to detect the cell apoptosis and cell cycle in sertoli cells. RESULTS: The results showed that testicular protein PHGDH was down-regulated in patients w...