Abstract
Melatonin and Nrf2 signaling synergistically improve mammalian oocyte maturation and embryonic development. Furthermore, previous studies have suggested an interplay between peroxisomes and Nrf2 signaling in cells, but it is still unclear whether peroxisomes are involved in oocyte maturation. The aim of the present study was to identify the possible roles of peroxisomes in the melatonin-Nrf2 signaling pathway during in vitro maturation (IVM) of porcine oocytes. Porcine oocytes were treated with melatonin (10−9 M) and brusatol, a Nrf2 specific inhibitor, in order to investigate the mechanism. Then, the rates of maturation and related gene and protein expression were analyzed. During oocyte maturation, melatonin upregulated the expression of gene and protein related to Nrf2 signaling and peroxisomal activities; RNA sequencing partially validated these results. Our results demonstrate that melatonin can activate Nrf2 signaling by binding to melatonin receptor 2, resulting in the upregulation of catalase. Moreover, peroxisomes were also found to be activated in response to melatonin treatment, causing the activation of catalase; together with Nrf2 signaling, peroxisomes synergistically prevented the generation of reactive oxygen species and enhanced oocyte quality. Thus, we suggest that a crosstalk might exist between Nrf2 signaling and peroxisomal activities in porcine oocytes.
Highlights
Melatonin (N-acetyl-5-methoxytryptamine) is a natural hormone that is produced by the pineal gland in mammals and it is primarily known to be involved in the regulation of circadian rhythm [1]
Melatonin is known to crosstalk with signaling pathways that are related to oocyte maturation, embryo development, and the activation of antioxidant-related factors [7,8,9]; melatonin significantly upregulates lipid metabolism by increasing fatty acid content and lipid droplet size in porcine oocytes [9,10]
A similar decrease was observed in cumulus cells (CCs) expansion in the groups treated with 50, 200, and 400 nM brusatol compared to the control (Degree 1.07, 0.84, and 0.80 vs. Degree 3.094, respectively, p < 0.05) (Figure 1d)
Summary
Melatonin (N-acetyl-5-methoxytryptamine) is a natural hormone that is produced by the pineal gland in mammals and it is primarily known to be involved in the regulation of circadian rhythm [1]. Melatonin was found to exhibit antioxidant effects against elevated levels of reactive oxygen species (ROS) [4,5] that are known to be responsible for the development of several pathological conditions [6]. Several studies in the field of animal reproduction indicate that melatonin regulates antioxidant effects in porcine oocytes and embryos by preventing ROS-induced DNA damage. Melatonin is known to crosstalk with signaling pathways that are related to oocyte maturation, embryo development, and the activation of antioxidant-related factors [7,8,9]; melatonin significantly upregulates lipid metabolism by increasing fatty acid content and lipid droplet size in porcine oocytes [9,10]. The antioxidant mechanism of melatonin is regulated by nuclear factor erythroid 2-related factor 2 (Nrf2) signaling [8,11,12]
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