Mechanism of Methyltransferase METTL3 in Premature Ovarian Failure

Zhengmei PAN; Yanzhi WU; Chunyi SUN; Xiaoyujie GENG; Yang LIU

doi:10.12259/j.issn.2095-610X.S20250303

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Zhengmei PAN, Yanzhi WU, Chunyi SUN, Xiaoyujie GENG, Yang LIU. Mechanism of Methyltransferase METTL3 in Premature Ovarian Failure[J]. Journal of Kunming Medical University. doi: 10.12259/j.issn.2095-610X.S20250303

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Zhengmei PAN, Yanzhi WU, Chunyi SUN, Xiaoyujie GENG, Yang LIU. Mechanism of Methyltransferase METTL3 in Premature Ovarian Failure[J]. Journal of Kunming Medical University. doi: 10.12259/j.issn.2095-610X.S20250303

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Mechanism of Methyltransferase METTL3 in Premature Ovarian Failure

doi: 10.12259/j.issn.2095-610X.S20250303

1.
Department of Reproductive Medicine
2.
Department of Gynecology，The Second Affiliated Hospital of Kunming Medical University，Kunming Yunnan 650101，China

Received Date: 2024-09-01
Available Online: 2025-02-24

Abstract

Abstract

Objective To explore the mechanism of methyltransferase METTL3 in premature ovarian failure （POF） using a POF mouse model, providing a theoretical basis for the pathological research and clinical treatment of POF. Methods C57BL/6 female mice aged 6 to 8 weeks were selected for the study. The experimental group consisted of mice with a premature ovarian failure （POF） model established using the D-galactose metabolic method, while the control group comprised normal mice subjected to the same intervention with an equal volume of physiological saline. The levels of sex hormones were measured using ELISA, and histopathological changes in ovarian tissue were observed through HE staining to verify the successful establishment of the POF mouse model and to explore the correlation between METTL3 and POF at the tissue level. Additionally, stable transgenic mouse granulosa cell lines with METTL3 overexpression and knockdown were constructed at the cellular level. Cell proliferation and apoptosis were assessed using CCK-8 and FITC/PI dual staining methods to clarify the regulatory role of METTL3 in granulosa cell apoptosis and its impact on the occurrence of POF. Results The POF mouse model was successfully established. TUNEL staining revealed a significant increase in apoptotic granulosa cells in the ovarian tissue of the POF group （P < 0.05）, which also exhibited high expression of METTL3. In cellular experiments, stable transcriptional cell lines of mouse granulosa cells with METTL3 overexpression and knockdown were successfully constructed. Upregulation of METTL3 expression promoted granulosa cell apoptosis and inhibited their proliferation （P < 0.05）. Conclusion METTL3 participates in the development of POF by promoting granulosa cell apoptosis.
- Premature ovarian failure,
- Mouse model,
- METTL3,
- Granulosa cell apoptosis

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