Journal of Animal Reproduction and Biotechnology (한국동물생명공학회지)

The Korean Society of Animal Reproduction and Biotechnology (한국동물생명공학회)
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Oocyte quality is closely linked to DRP1 derived-mitochondrial fission and mitophagy by the NAD+ biosynthesis in a postovulatory-aging model of pigs

  • Ji-Hyun Shin (Department of Biotechnology, Daegu University) ;
  • Seul-Gi Yang (DU Center for Infertility, Daegu University) ;
  • Hyo-Jin Park (Department of Biotechnology, Daegu University) ;
  • Deog-Bon Koo (Department of Biotechnology, Daegu University)
  • Received : 2024.03.18
  • Accepted : 2024.04.22
  • Published : 2024.06.30
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Abstract

Background: Post-ovulatory aging (POA) of oocytes is related to a decrease in the quality and quantity of oocytes caused by aging. Previous studies on the characteristics of POA have investigated injury to early embryonic developmental ability, but no information is available on its effects on mitochondrial fission and mitophagy-related responses. In this study, we aimed to elucidate the molecular mechanisms underlying mitochondrial fission and mitophagy in in vitro maturation (IVM) oocytes and a POA model based on RNA sequencing analysis. Methods: The POA model was obtained through an additional 24 h culture following the IVM of matured oocytes. NMN treatment was administered at a concentration of 25 μM during the oocyte culture process. We conducted MitoTracker staining and Western blot experiments to confirm changes in mitochondrial function between the IVM and POA groups. Additionally, comparative transcriptome analysis was performed to identify differentially expressed genes and associated changes in mitochondrial dynamics between porcine IVM and POA model oocytes. Results: In total, 32 common genes of apoptosis and 42 mitochondrial fission and function uniquely expressed genes were detected (≥ 1.5-fold change) in POA and porcine metaphase II oocytes, respectively. Functional analyses of mitochondrial fission, oxidative stress, mitophagy, autophagy, and cellular apoptosis were observed as the major changes in regulated biological processes for oocyte quality and maturation ability compared with the POA model. Additionally, we revealed that the activation of NAD+ by nicotinamide mononucleotide not only partly improved oocyte quality but also mitochondrial fission and mitophagy activation in the POA porcine model. Conclusions: In summary, our data indicate that mitochondrial fission and function play roles in controlling oxidative stress, mitophagy, and apoptosis during maturation in POA porcine oocytes. Additionally, we found that NAD+ biosynthesis is an important pathway that mediates the effects of DRP1-derived mitochondrial morphology, dynamic balance, and mitophagy in the POA model.

Keywords

Acknowledgement

This research was supported by the National Research Foundation of Korea (NRF) funded by the Korean government (MSIT) (NRF-2021R1C1C2009469 and NRF2022R1A2C1002800), and the Basic Science Research Program through the NRF funded by the Ministry of Education (RS-2023-00246139), Republic of Korea.

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