Abstract
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 at which time, new transcription is halted. Oocytes then complete meiosis I, enter metaphase II, and arrest until fertilization, a process essential for egg competency and fertility. 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, leading some eggs to extrude two polar bodies and some to divide 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 extrusion. Surprisingly, single-egg sequencing revealed extensive differences in gene expression between wildtype and mos (-/-) eggs, including those with only one polar body. Many of the differentially expressed genes were involved in cell cycle regulation, including Aurka , Bub3 , and Cdk7 . Other upregulated pathways included metabolism of RNA, transcription, and neddylation. Furthermore, the gene expression profile of mos (-/-) eggs was markedly different from that of wildtype eggs chemically activated to undergo embryo-like divisions. 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.