Metabolomics reveals the toxicological effects of penconazole (PEN) in mice oocyte

Abstract

Penconazole (PEN) is a widely employed agent in the mitigation of fungal infestations, and recent research shows that water exposure and subsequent bioaccumulation within the food web elicits inflammatory responses in certain vital organs. Nonetheless, the fundamental pathways through which PEN impacts the quality of oocytes remain inadequately elucidated to date. We gavaged mouse with PEN (2.5 mg / kg) at the same time for 10 consecutive days and discovered a precipitous decline in the developmental proportion of oocytes collected from mice exposed to PEN. Metabolomic profiling revealed significant perturbations in key metabolic pathways, including oxidative phosphorylation and longevity regulation, with nicotinamide adenine dinucleotide (NAD) being markedly downregulated in PEN-exposed oocytes. Subsequent evaluations indicated a compromised state in both the cytoplasmic and nuclear maturation processes. This phenomenon stems from heightened levels of reactive oxygen species coupled with diminished mitochondrial functionality. Furthermore, Annexin-V signaling suggested that PEN triggered an apoptotic response in the oocytes. Our metabolomic findings underscore the central role of NAD depletion in mediating PEN-induced toxicity, linking mitochondrial dysfunction and oxidative stress to impaired oocyte quality. Overall, we recommend that females who are preparing for pregnancy in areas with higher risks of PEN exposure should supplement with Nicotinamide mononucleotide (NMN) to protect the quality of their oocytes.