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Journal Article Ppublish 10 citations

PubMed: 38426218 DOI: 10.1111/cpr.13626

NEK2 plays an essential role in porcine embryonic development by maintaining mitotic division and DNA damage response via the Wnt/β-catenin signalling pathway.

Cell Prolif 57(8):e13626

Authors: Se-Been Jeon, Pil-Soo Jeong, Hyo-Gu Kang, Min Ju Kim, Ji Hyeon Yun, Kyung Seob Lim, Bong-Seok Song, Sun-Uk Kim, Seong-Keun Cho, Bo-Woong Sim

Affiliations

  • Futuristic Animal Resource & Research Center (FARRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Republic of Korea. Department of Animal Science, College of Natural Resources & Life Science, Pusan National University, Miryang, Republic of Korea.
  • Futuristic Animal Resource & Research Center (FARRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Republic of Korea.
  • Futuristic Animal Resource & Research Center (FARRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Republic of Korea. Department of Animal Science and Biotechnology, College of Agriculture and Life Science, Chungnam National University, Daejeon, Republic of Korea.
  • Futuristic Animal Resource & Research Center (FARRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Republic of Korea. Department of Animal BioScience, School of Animal Life Convergence, Hankyong National University, Ansung, Republic of Korea.
  • Futuristic Animal Resource & Research Center (FARRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Republic of Korea. Department of Functional Genomics, University of Science and Technology, Daejeon, Republic of Korea.
  • Department of Animal Science, Life and Industry Convergence Research Institute (RICRI), College of Natural Resources & Life Science, Pusan National University, Miryang, Republic of Korea.

Abstract

NIMA-related kinase 2 (NEK2) is a serine/threonine protein kinase that regulates mitosis and plays pivotal roles in cell cycle regulation and DNA damage repair. However, its function in porcine embryonic development is unknown. In this study, we used an NEK2-specific inhibitor, JH295 (JH), to investigate the role of NEK2 in embryonic development and the underlying regulatory mechanisms. Inhibition of NEK2 after parthenogenesis activation or in vitro fertilization significantly reduced the rates of cleavage and blastocyst formation, the numbers of trophectoderm and total cells and the cellular survival rate compared with the control condition. NEK2 inhibition delayed cell cycle progression at all stages from interphase to cytokinesis during the first mitotic division; it caused abnormal nuclear morphology in two- and four-cell stage embryos. Additionally, NEK2 inhibition significantly increased DNA damage and apoptosis, and it altered the expression levels of DNA damage repair- and apoptosis-related genes. Intriguingly, NEK2 inhibition downregulated the expression of β-catenin and its downstream target genes. To validate the relationship between Wnt/β-catenin signalling and NEK2 during porcine embryonic development, we cultured porcine embryos in JH-treated medium with or without CHIR99021, a Wnt activator. CHIR99021 co-treatment strongly restored the developmental parameters reduced by NEK2 inhibition to control levels. Our findings suggest that NEK2 plays an essential role in porcine embryonic development by regulating DNA damage repair and normal mitotic division via the Wnt/β-catenin signalling pathway.

MeSH

Cell Cycle, Apoptosis, Cell Differentiation, Cells, Protein Serine-Threonine Kinases, Embryonic Development, Genes, Catenins, Dna Damage, Nima-Related Kinases

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