Glutathione protects against the meiotic defects of ovine oocytes induced by arsenic exposure via the inhibition of mitochondrial dysfunctions

Abstract

Accumulating evidences revealed the connections between arsenic exposure and mitochondrial dysfunctions induced reproductive toxicology. Meanwhile, production declines were found in livestock suffering from arsenic exposure. However, the connections between arsenic exposure and livestock meiotic defects remain unclear. In this study, the effects of sodium arsenite (NaAsO2) exposure during the in vitro maturation (IVM) on the meiotic potentials of ovine oocytes were analyzed. Furthermore, the effects of glutathione (GSH) supplementation on the meiotic defects of NaAsO2 exposed ovine oocytes were investigated by the assay of nuclear maturation, spindle organization, chromosome alignment, cytoskeleton assembly, cortical granule (CGs) dynamics, mitochondrial dysfunctions, reactive oxygen species (ROS) accumulation, oxidative DNA damages, cellular apoptosis, epigenetic modifications and fertilization capacities. The results showed that the meiotic defects of NaAsO2 exposed ovine oocytes were effectively ameliorated by the GSH supplementation via the inhibition of mitochondrial dysfunctions, which not only promoted the nuclear maturation, spindle organization, chromosome alignment, cytoskeleton assembly, CGs dynamic and fertilization capacities, but also inhibited the ROS accumulation, oxidative DNA damages and apoptosis of ovine MII oocytes. The abnormal expressions of 5mC, H3K4me3 and H3K9me3 in NaAsO2 exposed ovine oocytes, indicating the abnormal epimutations of DNA methylation and histone methylation, were also effectively ameliorated by the GSH supplementation. Taken together, this study confirmed the connections between arsenic exposure and meiotic defects of ovine oocytes. Meanwhile, the effects of GSH supplementation on the developmental competence of livestock oocytes, especially for these suffering from arsenic exposure were also founded, benefiting the extended researches for the GSH applications.

Keywords

• Glutathione
• Sodium arsenite
• Mitochondrial dysfunctions
• Oxidative stress
• Epigenetic modifications