Disrupted MOS signaling alters meiotic cell cycle regulation and the egg transcriptome

in Reproduction
Authors:
Gisela Cairo Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA

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Olha Kholod Thayer School of Engineering at Dartmouth, Hanover, New Hampshire, USA

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Olivia Palmer Thayer School of Engineering at Dartmouth, Hanover, New Hampshire, USA

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Sophia Meytin Thayer School of Engineering at Dartmouth, Hanover, New Hampshire, USA

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Brittany A Goods Thayer School of Engineering at Dartmouth, Hanover, New Hampshire, USA
Molecular and Systems Biology, and Program in Quantitative Biomedical Data Sciences, Hanover, New Hampshire USA

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https://orcid.org/0000-0002-5962-9570
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Soni Lacefield Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA

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https://orcid.org/0000-0002-2862-5067

Correspondence should be addressed to B A Goods: Britt.anne.goods@dartmouth.edu or to S Lacefield: Soni.Lacefield@dartmouth.edu
DOI:
https://doi.org/10.1530/REP-25-0156
Volume/Issue:
Volume 170: Issue 1
Article ID:
e250156
Article Type:
Research Article
Online Publication Date:
09 Jun 2025
Copyright:
© the author(s) 2025
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In brief

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.

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. 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.

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Print ISSN:
1470-1626
Online ISSN:
1741-7899

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