3-Nitropropionic acid exposure inhibits embyro development by disrupting mitochondrial function and inducing oxidative stress.

3-Nitropropionic acid (3-NP) is a naturally occurring mycotoxin produced by various species of fungi and plants. However, the potential impact of 3-NP exposure on reproductive health remains unclear. To address this gap, we conducted an in vitro study to investigate the toxic effects of 3-NP on the developmental processes of mouse embryos. The results showed that embryos exposed to 50 μM 3-NP exhibited significant pre-implantation developmental arrest. Notably, most embryos were stalled at the 2-cell stage, indicating disruption of the normal developmental processes. Further analysis showed exposure to 3-NP altered embryonic gene expression, disrupted zygotic genome activation (ZGA) and maternal gene degradation (MGD), and therefore inhibited maternal-zygote transition (MZT). Moreover, 3-NP exposure led to mitochondrial dysfunction, which not only impaired cellular energy metabolism but also induced substantial intracellular oxidative stress, resulting in increased DNA damage. Additionally, we observed that 3-NP exposure caused alterations in embryonic epigenetic modifications, particularly the aberrant upregulation of histone methylation levels, including elevated H3K27me3 and H3K9me3, which are closely linked to gene expression silencing. In summary, the present study reveals the in vitro toxic effects of 3-NP on the developmental function of mouse embryos, suggesting potential adverse effects of 3-NP exposure on female reproductive health.