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<p>Maternal effect genes (MEGs) produce factors that accumulate in oocytes and play critical roles in embryo development. Mutations of MEGs are frequently linked to reproductive and congenital disorders. The majority of identified mammalian MEGs encode epigenetic factors and RNA regulators. Here, we identify a MEG encoding the transcription factor Thanatos-associated protein 1 (<i>Thap1</i>). <i>Thap1</i> is highly expressed in mouse oocytes and early embryos. Oocyte-specific deletion of <i>Thap1</i> results in delayed progression of mouse embryos from the 1-cell to the 2-cell stage and 1-2-cell arrest, accompanied by defective zygotic genome activation (ZGA) and strongly impaired female fertility. Mechanistically, THAP1 activates a critical subset of genes in oocytes, including <i>Rrm1</i>, which produces ribonucleotide reductase required for generating deoxynucleotide triphosphates (dNTPs). Low-input metabolome profiling across 7 stages during the oocyte-to-embryo transition shows gradual, THAP1-dependent dNTP accumulation that peaks in MII oocytes. Overexpression of <i>Rrm1</i> in zygotes almost fully restores the 2-cell progression and ZGA in <i>Thap1</i> maternal-knockout embryos. Our findings identify THAP1 as a key maternal effector critical for the earliest stage of mammalian development.</p>

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THAP1 is a maternal effect factor required for the first cell cycle via Rrm1 in early mouse embryos

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月23日

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  • Qiang Fan,
  • Xi Wu,
  • Yanna Dang,
  • Lijun Dong,
  • Wenying Wang,
  • Feng Kong,
  • Lijuan Wang,
  • Xukun Lu,
  • Boyang Liu,
  • Shuyan Ji,
  • Wei Xie

摘要

Maternal effect genes (MEGs) produce factors that accumulate in oocytes and play critical roles in embryo development. Mutations of MEGs are frequently linked to reproductive and congenital disorders. The majority of identified mammalian MEGs encode epigenetic factors and RNA regulators. Here, we identify a MEG encoding the transcription factor Thanatos-associated protein 1 (Thap1). Thap1 is highly expressed in mouse oocytes and early embryos. Oocyte-specific deletion of Thap1 results in delayed progression of mouse embryos from the 1-cell to the 2-cell stage and 1-2-cell arrest, accompanied by defective zygotic genome activation (ZGA) and strongly impaired female fertility. Mechanistically, THAP1 activates a critical subset of genes in oocytes, including Rrm1, which produces ribonucleotide reductase required for generating deoxynucleotide triphosphates (dNTPs). Low-input metabolome profiling across 7 stages during the oocyte-to-embryo transition shows gradual, THAP1-dependent dNTP accumulation that peaks in MII oocytes. Overexpression of Rrm1 in zygotes almost fully restores the 2-cell progression and ZGA in Thap1 maternal-knockout embryos. Our findings identify THAP1 as a key maternal effector critical for the earliest stage of mammalian development.