In utero exposure of green coffee extract alters rat fetal neurodevelopment in a dose dependent manner

Abstract

Green coffee consumption has gained wide popularity, possibly due to its strong antioxidative activities and many beneficial effects in various human diseases. However, the effect of green coffee extract consumption on the development of the fetal central nervous system during pregnancy has not been elucidated. Consequently, the present study aimed to evaluate the effect of maternal administration of some doses of the green coffee extract on the development of the cerebral cortex, cerebellum, and spinal cord of rat fetuses in terms of histopathological, proliferation, astrogliosis, and ultrastructural investigations. Pregnant dams were divided into four groups; control group (administered distilled water) and three groups orally administered three different doses of green coffee extract, GC1 (200 mg/kg), GC2 (400 mg/kg), and GC3 (600 mg/kg) from the sixth day to the 15 th day of gestation.On the 20 th day, dams were sacrificed and fetal cerebral cortex, cerebellum, and spinal cord from different groups were fixed for subsequent investigations. The results showed that green coffee extract induced various histopathological changes in the three investigated organs including pyknosis, hemorrhage, and vacuolation.Immunohistochemical investigation revealed that green coffee extract decreased neuronal proliferation and increased reactive astrogliosis. Ultrastructurally, green coffee extract caused cytoplasmic rarefaction, neuronal degeneration, macrophage activation, and axon degeneration. Interestingly, the neurotoxic effects of green coffee on neuronal development were dose-dependent. Based on these results, the consumption of high doses of green coffee during pregnancy should be restricted. Moreover, further studies are needed to evaluate the long-term effects of green coffee ingestion on neuronal cognition and behavioral outcomes.