Ca2+ ionophore A23187 inhibits ATP generation reducing mouse sperm motility and PKA-dependent phosphorylation. (October 2020)

• Record Type: Journal Article
• Authors: Yang, Qiangzhen; Wen, Yi; Wang, Lirui; Peng, Zijun; Yeerken, Ranna; Zhen, Linqing; Li, Peifei; Li, Xinhong
• Is Part Of: Tissue & cell. Volume 66(2020)
• Publication Date: 2020-10
• Subjects: Calcium -- A23187 -- Sperm -- ATP -- Phosphorylation; Cytology -- Periodicals; 571.5
• DOI: 10.1016/j.tice.2020.101381
• Languages: English
• ISSNs: 0040-8166

Abstract

Highlights: A23187 induces Ca 2+ flux in sperm tail and not destroy the structure. Ca 2+ inhibits key energy-production enzymes' activities. A23187 inhibits mitochondrial membrane potential and ATP. Abstract: Male infertility is a global problem in modern society of which capacitating defects are a major cause. Previous studies have demonstrated that Ca 2+ ionophore A23187 can make mouse sperm capable of fertilizing in vitro, which may aid in clinical treatment of capacitating defects. However, the detailed role and mechanism of Ca 2+ in the capacitating process are still unclear especially how A23187 quickly renders sperm immotile and inhibits cAMP/PKA-mediated phosphorylation. We report that A23187 induces a Ca 2+ flux in the mitochondria enriched sperm tail and excess Ca 2+ inhibits key metabolic enzymes involved in acetyl-CoA biosynthesis, TCA cycle and electron transport chain pathways resulting in reduced ATP and overall energy production, however this flux does not destroy the structure of the sperm tail. Due to the decrease in ATP production, which is the main phosphate group donator and the power of sperm, the sperm is rendered immobile and PKA-mediated phosphorylation is inhibited. Our study proposed a possible mechanism through which A23187 reduces sperm motility and PKA-mediated phosphorylation from ATP generation, thus providing basic data for exploring the functional roles of Ca 2+ in sperm in the future.