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

Area of Science:

• Reproductive Toxicology
• Cellular Biology
• Environmental Health

Background:

• Microcystin-LR (MC-LR) is a cyanobacterial toxin known for reproductive toxicity.
• MC-LR induces oxidative stress and mitochondrial damage in granulosa cells, leading to follicle atresia and subfertility.

Purpose of the Study:

• To investigate the effects of MC-LR on mitochondrial morphology and glucose metabolism in granulosa cells.
• To elucidate the molecular mechanisms underlying MC-LR-induced female reproductive toxicity.

Main Methods:

• Granulosa cells were exposed to varying concentrations of MC-LR (0-1 μM).
• Mitochondrial morphology and dynamics were assessed using transmission electron microscopy and DRP1 expression analysis.
• Glucose uptake and glucose transporter (GLUT1, GLUT4) expression were evaluated.
• Reactive oxygen species (ROS) and FOXM1 levels were measured.

Main Results:

• MC-LR exposure led to mitochondrial fragmentation, characterized by increased DRP1-mediated mitochondrial fission.
• Glucose intake and expression of GLUT1 and GLUT4 were significantly decreased in MC-LR-treated cells.
• MC-LR exposure elevated ROS production and increased FOXM1 expression.

Conclusions:

• MC-LR exposure induces mitochondrial fragmentation and impairs glucose uptake in granulosa cells.
• Increased mitochondrial fission and oxidative stress are key mechanisms in MC-LR's reproductive toxicity.
• These findings offer new insights into the molecular pathways of MC-LR-induced female subfertility.