Maternal exposure to advanced oxidation protein products induces neurodevelopmental abnormalities in the offspring of mice.

Preeclampsia (PE) not only causes multi-organ damage to the mother but also exerts long-term effects on the development of the offspring. Prenatal exposure to PE has been demonstrated to result in deleterious neurodevelopment and behavioral abnormalities in the offspring. Our prior research has evidenced that advanced oxidation protein products (AOPPs), both the biomarker and promoter of oxidative stress, contribute to the pathogenesis of preeclampsia by inducing trophoblast dysfunction and systemic inflammation. However, it remains unclear whether offspring mice exposed to placental oxidative stress and dysfunction induced by AOPPs will exhibit abnormal neurodevelopment and the underlying mechanisms involved. In this study, we found pregnant mice injected with AOPPs and AOPPs-induced sEVs exhibited PE-like symptoms with elevated blood pressure and reduced fetal weight. Furthermore, behavioral detection showed that male and female adult offspring mice exposed to AOPPs prenatally displayed impairments in learning and memory. Placental and hippocampal transcriptome sequencing revealed that inflammation and immune response may play a pivotal role in this process. Our study provides valuable insights into the pathogenesis of adverse neurodevelopment and cognitive dysfunction in offspring exposed to placental oxidative stress induced by AOPPs and the search for effective preventive and therapeutic measures.