(76) The Notch Signaling Pathway is Important for Porcine Meiotic Progression

Pil-Soo Jeong¹; Se-Been Jeon¹; Hyo-Gu Kang¹; Min Ju Kim¹; Ji Hyeon Yun¹; Eun Young Choi¹; Bong-Seok Song¹; Sun-Uk Kim^1,2; Bo-Woong Sim^1,2

1. Futuristic Animal Resource & Research Center (FARRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Republic of Korea

2. Department of Functional Genomics, University of Science and Technology (UST), Daejeon, Republic of Korea

Abstract Text:

The Notch signaling pathway plays an important role in ovarian follicle development in mammals. However, the exact role of the Notch signaling pathway during oocyte maturation has not been studied. In this study, we used a γ-secretase inhibitor, RO4929097 (RO), to elucidate the role of the Notch signaling pathway in porcine oocyte maturation. RO treatment significantly decreased the proportion of complete cumulus expansion and metaphase II oocytes in a dose-dependent manner. Although some of the RO-treated oocytes progressed to metaphase II stage, these oocytes exhibited a significantly higher incidence of aneuploidy and a greater proportion of abnormal actin morphology than those of the control. RO-treated oocytes had a significantly higher proportion of oocytes with aberrant spindles or misaligned chromosomes, an increased number of lagging chromosomes, and a decrease in acetylated tubulin levels. With regard to cytoplasmic maturation, RO treatment resulted in a significant reduction in mitochondrial content, the proportion of normal mitochondrial distribution, mitochondrial membrane potential, and ATP content, as well as endoplasmic reticulum (ER) content, the proportion of normal ER distribution, and calcium homeostasis compared with the control. In addition, the RO-treated oocytes had impaired developmental competence in terms of cleavage rate, blastocyst formation rate, proportion of expanded blastocyst, cell number, and cell survival rate compared to the control. These findings suggest that Notch signaling plays an important role in porcine oocyte maturation by regulating microtubule function, including spindle organization and chromosome segregation, and supports proper oocyte cytoplasmic maturation by maintaining homeostasis of the mitochondrial and ER systems.

This research was supported by the Korea Research Institute of Bioscience and Biotechnology (KRIBB) Research Initiative Program (KGM4252533, KGM5382531), Republic of Korea.