Melatonin-Nrf2 Signaling Activates Peroxisomal Activities in Porcine Cumulus Cell-Oocyte Complexes

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.