Mechanism Of Microcystin-LR Led To Mitochondrial Dysfunction And Reduced Glucose Intake In Ovarian Granulosa Cells

Microcystins(MCs)is a cyclic heptapeptide intracellular endotoxins released by cyanobacteri.MCs has a variety of variants,one of which,Microcystin-LR(MC-LR),is the most toxic and widely distributed.Our laboratory was the first to find that MCLR induced oxidative stress in mouse ovarian granulosa cells(GCs),which ultimately led to follicular atresia and decreased reproductive capacity.It has also been reported that MC-LR causes oxidative stress in GCs by damaging mitochondrial structures.However,the mechanism by which MC-LR induces mitochondrial structural damage remains unclear.In this study,female ovarian GCs of mice were used as research objects to observe the effects of MC-LR on mitochondrial structure,dynamics and glucose metabolism,and to explore the mechanism.In this study,GCs were exposed different dose of MC-LR for 24 h.Exposure to MC-LR led to GCs apoptosis,slow follicle growth,mitochondrial swelling and cristae rupture.FOXM1 increased significantly after exposure to MC-LR due to ROS overproduction.FOXM1 enters the nucleus and upregulates DRP1.DRP1 ultimately leads to a decrease of glucose metabolism in GCs by downregulating GLUT1 and GLUT4.In conclusion,this study provides further experimental evidence for understanding the mechanism by which MC-LR induces ovarian GCs dysfunction.