ArticleMolecular therapy. Nucleic acids2025
SHMT2 is essential for mammalian preimplantation embryonic development through
Article in Molecular therapy. Nucleic acids, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Research and application advances in real-time single-cell functional analysis.Discover nano · 2026Review
- Serine Hydroxymethyltransferase (SHMT) in biology and disease: molecular mechanisms and therapeutic targeting.Journal of translational medicine · 2026Review
- Amino Acid Metabolic Enzymes in Gastric Cancer: Roles and Mechanisms in Tumorigenesis and Progression.Oncology research · 2026Review
- The Expression ofCells · 2025Article
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11 authors.
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Abstract
Assisted reproductive technology (ART) is used widely and efficiently to treat infertility. During the ART procedure, one of the main factors affecting the success rate is abnormal development of preimplantation embryos. The establishment and maintenance of developmental competence are precisely regulated at different levels, while minor errors at early stages may result in adverse outcomes, including developmental arrest and implantation failure. As one of the major inputs, the regulatory mechanisms of metabolites in embryonic development are less known. In this study, we investigated the functional relevance of the metabolic enzyme serine hydroxymethyltransferase 2 (SHMT2) and deoxyribonucleotide (dNTP) metabolites in mouse preimplantation embryonic development. By using a well-characterized SHMT2 inhibitor, SHMT-IN-2, we effectively inhibited the catalytic activity of the SHMT2 enzyme, which led to developmental arrest at the pronuclear stage of the embryo. A low-input liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and applied for detecting dNTP content in embryos. We found that SHMT2 inhibition led to an insufficient dTTP supply and replication stress during the first mitotic cleavage, thereby causing failure of pronuclear fusion and developmental arrest. Our findings demonstrate a specific mechanism where, apart from building blocks of DNA, the availability of dNTPs contributes to the control of mouse preimplantation embryonic development.
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