The mechanisms of mitochondrial dysfunction and glucose intake decrease induced by Microcystin-LR in ovarian granulosa cells

Abstract

Microcystin-LR (MC-LR) is a cyclic heptapeptide; it is an intracellular toxin released by cyanobacteria that exhibits strong reproductive toxicity. Previous studies have demonstrated that MC-LR induces oxidative stress in granulosa cells by damaging the mitochondria, which eventually leads to follicle atresia and female subfertility. In the present study, granulosa cells were exposed to 0, 0.01, 0.1 and 1 μM MC-LR. After 24 h, we observed changes in mitochondrial cristae morphology and dynamics by analyzing the results of mitochondrial transmission electron microscopy and detecting the expression of DRP1. We also evaluated glucose intake using biochemical assays and expression of glucose transport related proteins. MC-LR exposure resulted in mitochondrial fragmentation and glucose intake decrease in granulosa cells, as shown by increasing mitochondrial fission via dynamin-related protein 1 (DRP1) upregulation and decreasing glucose transporter 1 and 4 (GLUT1 and GLUT4). Furthermore, the expression levels of forkhead box protein M1 (FOXM1) significantly increased due to the overproduction of reactive oxygen species (ROS) after MC-LR exposure. Our results proved that MC-LR exposure causes mitochondrial fragmentation and glucose intake decrease in granulosa cells, which provides new insights to study the molecular mechanism of female reproductive toxicity induced by MC-LR.

Keywords: Dynamin-related protein 1; Forkhead box protein M1; Granulosa cells; Microcystin-LR; Mitochondria.