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

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

  • Ecotoxicol Environ Saf. 2021 Apr 1;212:111931. doi: 10.1016/j.ecoenv.2021.111931.
Jinling Zhu 1 Kunyang Liu 1 Ligang Pei 2 Xinyue Hu 1 Yuchen Cai 1 Jie Ding 1 Dongmei Li 1 Xiaodong Han 3 Jiang Wu 4
Affiliations

Affiliations

  • 1 Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing 210093, China.
  • 2 Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, China.
  • 3 Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing 210093, China. Electronic address: hanxd@nju.edu.cn.
  • 4 Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing 210093, China. Electronic address: wujiang@nju.edu.cn.
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.

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