Glutathione ameliorates the meiotic defects of copper exposed ovine oocytes via inhibiting the mitochondrial dysfunctions

Jingyu Ren; Biao Wang; Liping Li; Shubin Li; Yuzhen Ma; Liya Su; Gang Liu; Yongbin Liu; Yanfeng Dai

doi:10.1016/j.ecoenv.2023.114530

Glutathione ameliorates the meiotic defects of copper exposed ovine oocytes via inhibiting the mitochondrial dysfunctions

Ecotoxicol Environ Saf. 2023 Feb:251:114530. doi: 10.1016/j.ecoenv.2023.114530. Epub 2023 Jan 9.

Authors

Jingyu Ren¹, Biao Wang², Liping Li¹, Shubin Li³, Yuzhen Ma³, Liya Su⁴, Gang Liu⁵, Yongbin Liu⁶, Yanfeng Dai⁷

Affiliations

¹ College of Life Science, Inner Mongolia University, No. 235 West Univ. Road, Hohhot, Zip Code: 010021, Inner Mongolia, China.
² Animal Husbandry Institute, Inner Mongolia Academy of Agricultural & Animal Husbandry Sciences, No. 22 Zhaowuda Road, Hohhot, Zip Code: 010031, Inner Mongolia, China.
³ Center of Reproductive Medicine, Inner Mongolia People's Hospital, No. 20 Zhaowuda Road, Hohhot, Zip Code: 010021, Inner Mongolia, China.
⁴ Key Laboratory of Medical Cell Biology, Clinical Medicine Research Center, Affiliated Hospital of Inner Mongolia Medical University, No. 1 Tongdao North Street, Hohhot, Zip Code: 010050, Inner Mongolia, China.
⁵ Key Laboratory of Medical Cell Biology, Clinical Medicine Research Center, Affiliated Hospital of Inner Mongolia Medical University, No. 1 Tongdao North Street, Hohhot, Zip Code: 010050, Inner Mongolia, China. Electronic address: 20190043@immu.edu.cn.
⁶ College of Life Science, Inner Mongolia University, No. 235 West Univ. Road, Hohhot, Zip Code: 010021, Inner Mongolia, China. Electronic address: ybliu@imu.edu.cn.
⁷ College of Life Science, Inner Mongolia University, No. 235 West Univ. Road, Hohhot, Zip Code: 010021, Inner Mongolia, China. Electronic address: daiyf@imu.edu.cn.

PMID: 36630773
DOI: 10.1016/j.ecoenv.2023.114530

Abstract

Regardless of the essential role of copper (Cu) in the physiological regulation process of mammalian reproduction, excessive exposure to Cu triggers the meiotic defects of porcine oocytes via compromising the mitochondrial functions. However, the connections between the excessive Cu exposure and meiotic defects of ovine oocytes have not been reported. In this study, the effect of copper sulfate (CuSO₄) exposure on the meiotic potentials of ovine oocytes was analyzed. Subsequently, the ameliorative effect of glutathione (GSH) supplementation on the meiotic defects of CuSO₄ exposed ovine oocytes was investigated. For these purposes, the in vitro maturation (IVM) of ovine cumulus oocyte complexes (COCs) was conducted in the presence of 5, 10, 20 and 40 μg/mL of CuSO₄ supplementation. Subsequently, different concentrations of GSH (2, 4 and 8 mM) were added to the IVM medium containing CuSO₄ solution. After IVM, the assay, including nuclear maturation, spindle organization, chromosome alignment, cytoskeleton assembly, cortical granule (CGs) dynamics, mitochondrial function, reactive oxygen species (ROS) generation, apoptosis, epigenetic modification and fertilization capacity of ovine oocytes were performed. The results showed that excessive Cu exposure triggered the meiotic defects of ovine oocytes via promoting the mitochondrial dysfunction related oxidative stress damage. Moreover, the GSH supplementation, not only ameliorated the decreased maturation potential and fertilization defect of CuSO₄ exposed oocytes, but inhibited the mitochondrial dysfunction related oxidative stress damage, ROS generation, apoptosis and altered H3K27me3 expression in the CuSO₄ exposed oocytes. Combined with the gene expression pattern, the finding in the present study provided fundamental bases for the ameliorative effect of GSH supplementation on the meiotic defects of CuSO₄ exposed oocytes via inhibiting the mitochondrial dysfunctions, further benefiting these potential applications of GSH supplementation in the mammalian IVM system and livestock breeding suffering from the excessive Cu exposure.

Keywords: Copper; Glutathione; H3K27me3; Meiotic defects; Mitochondrial dysfunctions.

MeSH terms

Animals
Copper* / metabolism
Glutathione / metabolism
Mammals / metabolism
Mitochondria
Oocytes*
Reactive Oxygen Species / metabolism
Sheep
Swine

Substances

Copper
Reactive Oxygen Species
Glutathione