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  • In mammals meiotic maturation is the

    2021-11-29

    In mammals, meiotic maturation is the process that couples completion of MI with the acquisition of developmental competence to support fertilization (Figure 1). In females there are several hallmark maturation events that are linked to the cell cycle. First, meiosis is not continuous, it is initiated during fetal development where DNA replication and homologous recombination occur, followed by a prolonged arrest at the dictyate stage of prophase I. During the arrest, oocyte growth occurs. This arrest lasts until the organism is reproductively mature, after which a subset of the oocytes will resume meiosis in response to species-specific regulatory cues. The second hallmark is that once oocytes reach full size, they cease transcription and remain silent throughout completion of meiosis, relying solely on mRNA transcribed during oocyte growth. Therefore, oocytes rely on recruitment of stored maternal transcripts to assist in completing meiosis and the subsequent developmental changes that take place in preimplantation embryos before zygotic genome activation [1]. Finally, vertebrate oocytes arrest at metaphase of MII, and will not complete MII until fertilized by sperm. It is crucial that the meiotic divisions occur accurately because errors in chromosome segregation can result in aneuploidy. Aneuploidies are frequently incompatible with life and are the leading genetic cause of infertility and failure of in vitro fertilization in humans [2]. Although biotin 100 mg is rare in most organisms, humans are particularly prone to chromosomal abnormalities, with 10–30% of fertilized eggs being aneuploid, accounting for nearly one third of miscarriages [2].
    Aurora Kinases The precise regulation of meiosis is a choreographed dance involving numerous proteins that ensure formation of a healthy gamete. The aurora kinases (AURKs) are a conserved family of protein kinases, key in coordinating this dance in mitosis and meiosis 3, 4, 5. The kinases act as molecular switches, regulating multiple processes in cell division including but not limited to; spindle organization, chromosome alignment, the spindle assembly checkpoint (SAC), the abscission checkpoint, and cytokinesis (Table 1) [3]. The mammalian genome encodes three AURK isoforms (aurora kinases A–C: AURKA, AURKB, and AURKC) (Figure 2, Key Figure). AURKA is expressed in mitotic and meiotic cells and localizes to spindle poles to regulate spindle mechanics 6, 7. AURKB is also expressed in mitosis and meiosis with dynamic protein localization: first localizing to chromosomes at metaphase where it regulates chromosome alignment and kinetochore–microtubule (K–MT) attachments, and then in anaphase localizing to the spindle midzone to assist in cytokinesis 3, 8, 9, 10. AURKC expression is primarily restricted to germ cells and has higher sequence similarity to AURKB than to AURKA 11, 12, 13. AURKC localization is a hybrid of AURKA and AURKB in mitosis because it localizes to spindle poles and chromosomes in metaphase, but to the spindle midzone in anaphase 14, 15, 16. Found only in mammals, AURKC may have arisen from a genome duplication event of an ancestral AURKB/C gene found in cold-blooded vertebrates [5]. The conservation of a third AURK in mammalian meiosis has been a mystery in gamete biology for decades. Why do gametes require the presence of an additional AURK compared to their mitotic counterparts? The unique MI division and prolonged periods of cell-cycle arrest make it enticing to imagine that a third AURK is required to mediate specific roles unique to oocyte meiotic maturation. Understanding these functions, and how AURKC interacts with the other two homologs, will be crucial for understanding the complex inner workings of meiosis and hopefully will shed light on why aneuploidies are so common in humans. The purpose of this review is to highlight current understanding of the functions of the AURKs in female meiosis, to speculate why meiotic cells use three AURKs, and to identify significant remaining questions in the field. To remain concise this review will not elaborate on the details of key regulatory pathways including spindle morphogenesis, the SAC, cytokinesis, and the abscission checkpoint. Many other reviews do a thorough job covering these topics in mitosis in detail, and instead we will focus on the known requirements for the aurora kinase family members as they relate to these pathways 10, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28.