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image of Trimethylamine N-oxide Impairs Oocyte Maturation and Embryogenesis via NF-κB/NLRP3 Pathway Modulation

Abstract

Background

The role of Trimethylamine N-oxide (TMAO) in oocyte maturation and embryogenesis remains unclear, particularly its impact on ovarian granulosa cells (OGCs) and its underlying mechanisms.

Methods

This study examined the effects of TMAO (100-400 µmol/L) on oocyte maturation, cumulus cell expansion, mitochondrial distribution, and embryonic development and in a BALB/c mouse model. The involvement of the NF-κB/NLRP3 signaling pathway in TMAO-induced ovarian dysfunction was assessed using Western blotting and gene expression analyses. The potential therapeutic effect of miRNA-146, an NF-κB inhibitor, was also explored.

Results

Western blotting confirmed that TMAO activates the NF-κB signaling pathway and induces the synthesis of caspase 3 and NLRP3 complexes. However, pretreatment with miRNA-146, an NF-κB inhibitor, significantly reduced inflammation and inflammatory gene expression during TMAO therapy. Additionally, miRNA-146 pretreatment promoted oocyte maturation by suppressing NF-κB/NLRP3 activation, OGCs apoptotic inflammatory factor expression, and the gene expression of NF-κB, caspase 3, and NLRP3.

Conclusion

Findings demonstrate that TMAO disrupts oocyte development through NF-κB/NLRP3 activation, contributing to ovarian dysfunction. Notably, targeting TMAO and its downstream signaling could serve as a novel therapeutic strategy for premature ovarian insufficiency (POI).

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2025-05-22
2025-09-13

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Trimethylamine N-oxide Impairs Oocyte Maturation and Embryogenesis via NF-κB/NLRP3 Pathway Modulation
Bentham Science Publishers ; https://doi.org/10.2174/0115680096364675250419135908
/content/journals/ccdt/10.2174/0115680096364675250419135908
/content/journals/ccdt/10.2174/0115680096364675250419135908
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  • Article Type:     Research Article
Keywords: premature ovarian insufficiency ; oocyte ; granulosa cell ; demonstrate ; Trimethylamine-N-oxide ; NF-κB/NLRP3 signaling pathway

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