Polo‐like kinase 1 inhibition results in misaligned chromosomes and aberrant spindles in porcine oocytes during the first meiotic division

Abstract

Polo-like kinase 1 (Plk1), a type of serine/threonine protein kinase, has been implicated in various functions in the regulation of mitotic processes. However, these kinase's roles in meiotic division are not fully understood, particularly in the meiotic maturation of porcine oocytes. In this study, the expression and spatiotemporal localization of Plk1 were initially assessed in the meiotic process of pig oocytes by utilizing Western blotting with immunofluorescent staining combined with confocal microscopy imaging technique. The results showed that Plk1 was expressed and exhibited a dynamic subcellular localization throughout the meiotic process. After germinal vesicle breakdown (GVBD), Plk1 was detected prominently around the condensed chromosomes and subsequently exhibited a similar subcellular localization to α-tubulin throughout subsequent meiotic phases, with particular enrichment being observed near spindle poles at MI and MII. Inhibition of Plk1 via a highly selective inhibitor, GSK461364, led to the failure of first polar body extrusion in porcine oocytes, with the majority of the treated oocytes being arrested in GVBD. Further subcellular structure examination results indicated that Plk1 inhibition caused the great majority of oocytes with spindle abnormalities and chromosome misalignment during the first meiotic division. The results of this study illustrate that Plk1 is critical for the first meiotic division in porcine oocytes through its influence on spindle organization and chromosome alignment, which further affects the ensuing meiotic cell cycle progression.

PLK1 is required for chromosome compaction and microtubule organization in mouse oocytes

“…Similar to work assessing the role of PLK1 in oocytes using siRNA and kinase inhibition approaches, we demonstrated that PLK1 is required for spindle integrity to ensure the formation of normal bipolar spindles capable of facilitating chromosome segregation during meiosis I ( Clift and Schuh, 2015 ; Solc et al. , 2015 ; Liao et al. , 2018 ).…”

ZWINT: A potential therapeutic biomarker in patients with glioblastoma correlates with cell proliferation and invasion

“…PLK1 and SKA1 are two newly discovered genes associated with mitosis and tumorigenesis. PLK1 encodes a serine/threonine protein kinase, which is a critical regulator of cell cycle progression, cytokinesis, mitosis and the DNA damage response (40). The deletion of the PLK1 protein dramatically inhibited cancer cell proliferation and induced apoptosis (41).…”

HDAC8 drives spindle organization during meiotic maturation of porcine oocytes

“…The accurate segregation of genetic information between daughter cells are the most fundamental processes of life and requires a molecular machine built primarily of microtubules that form a specialized bipolar‐shaped spindle to drive the congression of chromosomes at metaphase I (M I) stage and the segregation of chromosomes at anaphase I (A I) stage in cells 21‐24 . Thus, the precise spatiotemporal coordination of spindle assembly and chromosome alignment is essential for the orderly progression of oocyte maturation 25 . Any mistake during this process is prone to chromosome segregation errors that would result in the aneuploid eggs 26 .…”