Background Normal testicular development is essential for maintaining male fertility and reproductive performance in livestock.Leydig cells(LCs)play a central role in testicular physiology;however,the epigenetic mecha...Background Normal testicular development is essential for maintaining male fertility and reproductive performance in livestock.Leydig cells(LCs)play a central role in testicular physiology;however,the epigenetic mechanisms regulating their development remain largely unclear.Methyltransferase-like 3(METTL3),a key m^(6)A methylation enzyme,and micro RNAs are increasingly recognised as critical regulators of this process.Results METTL3 expression in goat LCs markedly decreased during testicular development.This downregulation reduced m^(6)A modification on pri-miR-145,impairing Di George syndrome critical region 8-mediated processing and resulting in decreased levels of mature mi R-145-3p.This reduction in mi R-145-3p increased the expression of phosphoenolpyruvate carboxykinase 1(PCK1),which activated gluconeogenesis,increased intracellular glucose levels,and increased mitochondrial membrane potential.Consequently,this metabolic shift upregulated cell cyclerelated genes(cyclin B1 and cyclin E2),promoting LC proliferation and testicular growth.Conclusions Our findings demonstrate that the METTL3/mi R-145-3p/PCK1 axis is a key regulatory pathway linking epigenetic modification to the metabolic activity and proliferation of LCs.This mechanism provides novel insights into the molecular control of testicular development in male goats and may offer new targets for improving male reproductive capacity in livestock.展开更多
基金supported by the National Natural Science Foundation of China(32260835)Guizhou High-level Innovative Talents Project(Qiankehe Platform Talents[2022]021-1)+2 种基金Guizhou Province Mutton Sheep Genetic Improvement and Innovative Utilization Science and Technology Innovation Talent Team Project(Qian Kehe Platform Talent-CXTD[2023]025)the Natural Science Special Research Fund of Guizhou University(Gui Da Te Gang He Zi[2025]12)Project on the Development of a Technical Support System for the Meat Sheep Industry in Guizhou Province(GZRYCYJSTX-02)。
文摘Background Normal testicular development is essential for maintaining male fertility and reproductive performance in livestock.Leydig cells(LCs)play a central role in testicular physiology;however,the epigenetic mechanisms regulating their development remain largely unclear.Methyltransferase-like 3(METTL3),a key m^(6)A methylation enzyme,and micro RNAs are increasingly recognised as critical regulators of this process.Results METTL3 expression in goat LCs markedly decreased during testicular development.This downregulation reduced m^(6)A modification on pri-miR-145,impairing Di George syndrome critical region 8-mediated processing and resulting in decreased levels of mature mi R-145-3p.This reduction in mi R-145-3p increased the expression of phosphoenolpyruvate carboxykinase 1(PCK1),which activated gluconeogenesis,increased intracellular glucose levels,and increased mitochondrial membrane potential.Consequently,this metabolic shift upregulated cell cyclerelated genes(cyclin B1 and cyclin E2),promoting LC proliferation and testicular growth.Conclusions Our findings demonstrate that the METTL3/mi R-145-3p/PCK1 axis is a key regulatory pathway linking epigenetic modification to the metabolic activity and proliferation of LCs.This mechanism provides novel insights into the molecular control of testicular development in male goats and may offer new targets for improving male reproductive capacity in livestock.
