Melatonin protects porcine oocyte from copper exposure potentially by reducing oxidative stress potentially through the Nrf2 pathway

Copper is widely used as a feeding additive to promote livestock growth. However, excessive copper can be excreted with feces, causing heavy metal pollution and aggravating environmental problems. At the same time, studies have found that excess copper can cause damage to reproductive function and reduce gamete quality. Here, we explored the effects of adding different concentrations of copper to the culture medium on porcine oocytes. First polar body extrusion rate, embryo development, and intracellular levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP) DJm, adenosine triphosphate(ATP) content, and acetylation of lysine 9 on histone H3 protein subunit (H3K9ac) were assessed. Results demonstrated that Cu exposure causes abnormalities in mitochondrial function and epigenetic modification, resulting in increased oxidative stress and levels of ROS, ultimately leading to a decreased porcine oocyte quality. In addition, we found melatonin can protect porcine oocytes from those damages. Notably, Nrf2 protein expression was significantly increased by copper exposure, meanwhile, Nrf2 signaling pathway inhibitor ML385 significantly attenuated the protective role of melatonin on oxidative stress induced by copper exposure. In summary, our study demonstrates that copper activates the Nrf2 pathway and impairs oocyte maturation by inducing oxidative stress, leading to poor quality of porcine oocytes, and the changes can be reversed by melatonin.(c) 2022 Elsevier Inc. All rights reserved.

Automated summary

This study investigated the effects of copper on porcine oocytes and revealed that copper leads to abnormalities in mitochondrial function and epigenetic modification, resulting in increased oxidative stress and levels of ROS, ultimately leading to decreased porcine oocyte quality. Melatonin can protect porcine oocytes from copper-induced damages, and copper activates the Nrf2 pathway, impairing oocyte maturation.