Cairo Gisela, Kholod Olha, Palmer Olivia, Meytin Sophia, Goods Brittany A, Lacefield Soni
Reproduction. 2025 Jun 9;170(1). doi: 10.1530/REP-25-0156. Print 2025 Jul 1.
Through the precise coordination of meiosis, the oocyte gives rise to a mature egg that is competent to support fertilization and initiate embryonic development. This study reveals that MOS signaling is critical for proper meiotic regulation and for maintaining the egg in a transcriptionally inactive state.
Mammalian female meiosis is tightly regulated to produce a developmentally competent egg. Oocytes enter meiosis in the fetal ovary and then arrest at prophase I until sexual maturation. Upon hormonal stimulation, a subset of oocytes resumes meiosis. Oocytes then complete meiosis I, enter metaphase II and arrest until fertilization, a process essential for egg competency. The MOS kinase is a key regulator of the metaphase II arrest, activating the MAPK signaling cascade. Loss of MOS in female mice disrupts the maintenance of the metaphase II arrest, with some eggs extruding two polar bodies and some dividing beyond anaphase II. To investigate the consequences of the Mos deletion, we performed live imaging and found that mos-/- eggs exhibit transient chromosome separation events in meiosis I, suggesting a role for MOS in coordinating the timing of meiotic divisions. Further analysis showed that new transcription is required for mos-/- eggs to undergo additional divisions but not for second polar body (PB) extrusion. Surprisingly, single-egg sequencing revealed extensive differences in gene expression between wild-type (WT) and mos-/- eggs, including those with only one PB. Many differentially expressed genes were involved in cell cycle regulation, including Aurka, Bub3 and Cdk7. Upregulated pathways included metabolism of RNA, transcription and neddylation. Furthermore, the gene expression profile of mos-/- eggs was markedly different from that of chemically activated WT eggs. Our findings demonstrate that MOS plays a crucial role in meiotic cell cycle regulation and helps ensure that the egg maintains the proper transcriptome necessary for developmental competence.
通过减数分裂的精确协调，卵母细胞产生一个成熟的卵子，该卵子有能力支持受精并启动胚胎发育。本研究表明，MOS信号对于适当的减数分裂调控以及使卵子维持转录非活性状态至关重要。
哺乳动物雌性减数分裂受到严格调控以产生具有发育能力的卵子。卵母细胞在胎儿卵巢中进入减数分裂，然后停滞在减数第一次分裂前期直至性成熟。在激素刺激下，一部分卵母细胞恢复减数分裂。卵母细胞随后完成减数第一次分裂，进入减数第二次分裂中期并停滞直至受精，这一过程对卵子的能力至关重要。MOS激酶是减数第二次分裂中期停滞的关键调节因子，可激活丝裂原活化蛋白激酶（MAPK）信号级联反应。雌性小鼠中MOS的缺失会破坏减数第二次分裂中期停滞的维持，一些卵子会排出两个极体，一些则会在减数第二次分裂后期之后继续分裂。为了研究Mos缺失的后果，我们进行了实时成像，发现mos-/-卵子在减数第一次分裂中表现出短暂的染色体分离事件，这表明MOS在协调减数分裂的时间方面发挥作用。进一步分析表明，mos-/-卵子进行额外分裂需要新的转录，但排出第二极体（PB）则不需要。令人惊讶的是，单卵测序揭示了野生型（WT）和mos-/-卵子之间基因表达的广泛差异，包括那些只有一个PB的卵子。许多差异表达基因参与细胞周期调控，包括极光激酶A（Aurka）、Bub3和细胞周期蛋白依赖性激酶7（Cdk7）。上调的通路包括RNA代谢、转录和NEDD化。此外，mos-/-卵子的基因表达谱与化学激活的WT卵子明显不同。我们的研究结果表明，MOS在减数分裂细胞周期调控中起关键作用，并有助于确保卵子维持发育能力所需的适当转录组。
