Resveratrol Protects against Zearalenone-Induced Mitochondrial Defects during Porcine Oocyte Maturation via PINK1/Parkin-Mediated Mitophagy

Abstract

Mitochondria hold redox homeostasis and energy metabolism as a crucial factor during oocyte maturation, while the exposure of estrogenic mycotoxin zearalenone causes developmental incapacity in porcine oocyte. This study aimed to reveal a potential resistance of phytoalexin resveratrol against zearalenone during porcine oocyte maturation and whether its mechanism was related with PTEN-induced kinase 1 (PINK1)/Parkin-mediated mitophagy. Porcine oocytes were exposed to 20 μM zearalenone with or without 2 μM resveratrol during in vitro maturation. As for the results, zearalenone impaired ultrastructure of mitochondria, causing mitochondrial depolarization, oxidative stress, apoptosis and embryonic developmental incapacity, in which mitophagy was induced in response to mitochondrial dysfunction. Phytoalexin resveratrol enhanced mitophagy through PINK1/Parkin in zearalenone-exposed oocytes, manifesting as enhanced mitophagy flux, upregulated PINK1, Parkin, microtubule-associated protein light-chain 3 beta-II (LC3B-II) and downregulated substrates mitofusin 2 (MFN2), voltage-dependent anion channels 1 (VDAC1) and p62 expressions. Resveratrol redressed zearalenone-induced mitochondrial depolarization, oxidative stress and apoptosis, and accelerated mitochondrial DNA copy during maturation, which improved embryonic development. This study offered an antitoxin solution during porcine oocyte maturation and revealed the involvement of PINK1/Parkin-mediated mitophagy, in which resveratrol mitigated zearalenone-induced embryonic developmental incapacity.

Smart-seq2 Technology Reveals a Novel Mechanism That Zearalenone Inhibits the In Vitro Maturation of Ovine Oocytes by Influencing TNFAIP6 Expression

“…Previous studies have shown that ZEN affects animal oocyte maturation mainly via the expression of genes involved in oocyte maturation, cumulus expansion factor, oxidative stress, cell apoptosis, autophagy, and spindle assembly checkpoint [9][10][11][12][13][14][15][16][17]. The overall transcriptome data analysis revealed that ZEN induced oxidative stress, promoted apoptosis and autophagy, and inhibited oocyte development and spindle assembly, thus impeding ovine oocyte IVM.…”

“…In pigs, ZEN can significantly increase the phosphatidylcholine or phosphatidylethanolamine content and consume hemolysin phosphatidylcholine, thereby impairing follicular cavity formation and oocyte maturation [11]. In mice and pigs, ZEN can increase oxidative stress and disrupt spindle assembly and chromosome separation, leading to premature condensation of chromatin and interfering with the expression of genes related to oocyte activity, spindle assembly, redox potential, and apoptosis, thereby inhibiting the discharge of polar bodies and cumulus expansion and affecting oocyte maturation [12,13]; it also causes autophagy, apoptosis, and oxidative stress and disrupts embryo development by affecting the expression of epigenetic histones and organelle structure and function (mitochondria, endoplasmic reticulum, Golgi apparatus, and lysosomes), in turn affecting oocyte maturation and ovarian follicle formation [14][15][16]. It has a damaging effect on preantral follicles in ovine ovaries and participates in oocyte autophagy, although the specific mechanism of toxicity is unknown [17].…”

Heme Oxygenase-1 Regulates Zearalenone-Induced Oxidative Stress and Apoptosis in Sheep Follicular Granulosa Cells

“…ZEA is one of the most common mycotoxins. Numerous studies have shown that it affects the reproductive capacity of animals [ 25 , 26 , 27 ]. The widespread distribution of ZEA in animal feed exposes farm animals to its toxic effects, which is a global public health problem [ 19 ].…”

Mechanisms of mitochondrial dysfunction in ovarian aging and potential interventions

“…CoQ10 significantly prevented aging-induced oxidative stress, and increased mitochondrial biogenesis (SIRT1 and PGC1α) and mitophagy (PINK1 and Parkin)-related proteins in postovulatory oocyte of pigs ( 104 ). Resveratrol can increase the expression of PINK1 and Parkin proteins regulate the autophagy ability of mitochondria, and protect ovarian function ( 175 ). Metformin and Melatonin are AMPK activators ( 105 , 174 ), which could increase intracellular calcium concentrations thereby increasing the induction of mitochondrial biogenesis through transcription factors (such as NRFs, TFAM) ( 111 ).…”