Alteration of Neurodevelopmental Gene Expression Following Prenatal Exposure to Aquatic Crocus Sativus L. Extract in Mice

Crocus sativus (saffron) is used since ancient times as a medicine and spice. Various studies have demonstrated its antioxidant, anticancer, and anti-inflammation properties. In folkloric Iranian medicine, saffron is known as an abortifacient agent and some investigations announced it as a teratogen. The current study aimed to investigate the C. sativus extract effect on the fetal brain. The NMRI female mice were randomly divided into the control group and three saffron aquatic extract treated groups (25, 50, and 100 mg/kg of saffron aquatic extract). The fetuses were treated during 7-12 days post coitum (dpc). The fetuses were morphologically evaluated. Fetal brain tissues were investigated by histology and real-time PCR for Foxg1, Foxa2, Wif1, and Fgf8 expression. We found that three treatments reduced the number of fetuses. Fetuses of 25 mg/kg treated were significantly heavier (P<0.001) and had shorter tails (P<0.001) than controls. No difference was observed among treated and control groups in histological prospect. Foxa2 and Wif1 expressions dose-dependently increased (P<0.0001), while Foxg1 mRNA level increased in 25 mg/kg treatment (P<0.0001). Fgf8 expression decreased significantly in 25 mg/kg and 50 mg/kg treatments (P<0.0001 and P<0.001, respectively). These findings suggested that although no difference was observed in the histology of the fetal brain, the alteration of mentioned genes could affect the cellular biochemistry, molecular structures, and cell types in the developing brain.