Abstract
ATP-binding cassette E1 (ABCE1) is a member of the ATP-binding cassette transporters and essential for diverse biological events regulating abroad range of biological functions including viral infection, cell proliferation, anti-apoptosis, translation initiation and ribosome biogenesis. Here, we discovered that Abce1 also plays indispensable roles in mouse oocyte meiotic progression. In the present study, we examined the expression, localization, and function of Abce1 during mouse oocyte meiotic maturation. Immunostaining and confocal microscopy identified that Abce1 localized as small dots in nucleus in germinal vesicle stage. After germinal vesicle breakdown, it dispersedly localized around the whole spindle apparatus. During the anaphase and telophase stages, Abce1 was just like a cap to localize around the two pole region of spindle but not the midbody and chromosome. Knockdown of Abce1 by specific siRNA injection delayed the resumption of meiosis (GVBD) and affected the extrusion of first polar body. Moreover, the process of spindle assembly and chromosome alignment were severely impaired. Abce1-RNAi led to the dissociation of γ-tubulin and p-MAPK from spindle poles, thus caused mounts of spindle morphology abnormities and chromosome alignment defects, leading to high incidence of aneuploidy. Our findings refresh the knowledge of Abce1 function by exploring its role in oocyte meiotic resumption, spindle assembly and chromosome alignment.
Highlights
In mammals, oocyte employs two extremely asymmetric divisions, meiosis I and meiosis II, with only one round of DNA replication thereon yielding the egg, a highly polarized gamate, which can wait the sperm for fertilization and execute a molecular program for development [1]
About 200 oocytes were used and the result showed that the expression of Abce1 in oocytes significantly increased from GV to metaphase I (MI) stage and later slightly declined in metaphase II (MII) stage. (Figure 1B)
Abce1 staining did not disperse into the cytoplasm as the microtubules did, big dots occurred around the chromosomes
Summary
Oocyte employs two extremely asymmetric divisions, meiosis I and meiosis II, with only one round of DNA replication thereon yielding the egg, a highly polarized gamate, which can wait the sperm for fertilization and execute a molecular program for development [1]. Chromosome alignment and segregation occur on a spindle-shaped structure that is built from microtubules. Defective structure of spindle and abnormal segregation of chromosome in meiosis could bring on aneuploidy. Mammalian oocytes are prone to chromosome segregation errors which can lead to aneuploid fetuses [2, 3]. Most embryonic aneuploidies in humans are incompatible with development, as for this reason, fetal aneuploidy is a major cause of pregnancy loss [4, 5]. To ensure orderly meiosis during oocyte maturation, spindle assembly and chromosome alignment must be accurately controlled
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