Prenatal stress increases learning and memory deficits in offspring: A toxicological study on hippocampal neuronal damage in rats

Background: Recent epidemiological studies have observed that prenatal stress induced learning and memory deficits in children, but the toxicological mechanisms remain unclear. Objectives: We conducted a systematic study to explore the toxicological mechanisms of prenatal stress on learning and memory in offspring. Methods: We established a prenatal stress model by corticosterone (CORT) administration at different dose levels (0, 10, 40 mg/kg) from gestational days 14-21. First we assessed hippocampal damage in the offspring by the neuronal damage, synaptic damage, and neurotransmitter levels. We then detected learning and memory ability by Morris water maze test, and finally we analyzed biomarkers of oxidative stress and apoptosis to explore the potential mechanism. Results: Prenatal stress induced by CORT administration was indicated by decreased body weight, increased serum CORT and reduced food consumption (p < 0.05). With prenatal stress increasing, hippocampal damage in the offspring worsened, characterized by damaged neurons, decreased synaptic proteins, and reduced neurotransmitters. Learning and memory deficits were observed, including long escape latency and increased travel distance to find the platform in the Morris water maze test (p < 0.05).The potential toxicological mechanisms underlying the learning and memory impairments were indicated by biomarkers: decreased antioxidant enzymes (SOD and T-AOC), increased pro-inflammatory cytokines (IL-6) and apoptosis (p < 0.05). Conclusion: Prenatal stress leads to hippocampus-dependent learning and memory impairments by neuron loss, synaptic injury, and reduced neurotransmitters. Our study implies that improving maternal well-being is helpful for the learning and memory development of the next generation.