Sevoflurane anesthesia in pregnant rats negatively affects nerve function in offspring potentially via inhibition of the Wnt/β-catenin pathway

Abstract

Due to the rapid development of medical technology used to perform intrauterine procedures during pregnancy, the number of patients receiving fetal surgery under general anesthesia is increasing. The aim of the present study was to determine the effects of anesthetics on the offspring of rats, and to identify the potential mechanisms underlying these effects. On day 14 of pregnancy, Sprague‑Dawley rats were equally divided into the following 3 groups (n=9): Control group (n=3), 3% sevoflurane group (n=3) and 4% sevoflurane group (n=3). Following birth of the offspring, the juvenile rats were assessed using an open‑field test, Morris water maze and a continuous passive avoidance test on different days to determine their learning abilities and memory. Western blot and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analyses were used to examine the expression of multiple critical factors associated with the proliferation and apoptosis of nerve cells, including Ki67, nestin, B cell leukemia/lymphoma 2 (Bcl-2), BCL2 associated X (Bax) and caspase‑3. Additionally, the level of adenosine triphosphate production among the 3 groups were compared. Furthermore, expression alterations in of glycogen synthase kinase‑3β (GSK‑3β) and β‑catenin were examined. The Morris water maze experiment revealed that an increased concentration of sevoflurane exposure significantly reduced the learning and memory abilities of the juvenile rats when compared with controls. In addition, western blotting and RT-qPCR analyses determined that the protein and mRNA expression levels of Bax, caspase‑3 and GSK‑3β were significantly increased relative to the controls. By contrast, the expression levels of nestin, Ki‑67, Bcl‑2 and β‑catenin were significantly reduced. The results of the present study suggest that exposure of pregnant mice to sevoflurane anesthesia demonstrates a negative effect on the learning and memory abilities of their offspring, and the Wnt/β-catenin signaling pathway may be involved in this process.