Caffeine interferes embryonic development through over-stimulating serotonergic system in chicken embryo

The potential harmful effects of caffeine in pregnant women aroused public interests due to its possibility to jeopardize fetal development. Monoamine neurotransmitters are thought to regulate neural development processes through maternal-fetal interactions, which may have long term impact on mental and behavioral effects. The current study focuses on investigating the effects of caffeine on the monoamine neurotransmitter system using developmental chicken embryos. The ED50 value of caffeine toxicity was 27.3 μmol/egg in chicken embryo. Administration of caffeine, with lower dosage than ED50 (2.5, 5.0 and 10.0 μmol/egg), caused failure of neural tube closure. In addition, contents of 5-HT and its metabolite 5-HIAA were increased under dosage of 10.0 μmol/egg caffeine administration. Gene expression of TPH2 was also increased by caffeine treatment. Caffeine could result in defect of neural tube closure and induce disorder of serotonergic system development, which may increase teratogenic rate of embryos. Meanwhile, it is probably an underlying factor for inducing psychological and behavioral disorders in adult. Moreover, caffeine was found to be accumulated in the embryonic brain and not being metabolized, which may incur a magnification of adverse effects. This study may provide valuable data for further investigations on toxicology of caffeine during different stages of pregnancy.

Graphical abstractDownload full-size imageHighlights► Abnormal closure of neural tubes was found in caffeine groups during early stage. ► Caffeine affects 5-HT in brain, which could be a factor for behavioral disorders. ► Elevation in 5-HT by caffeine could be due to the over-expression of TPH2. ► Caffeine accumulation in brain may augment its adverse effects at embryonic stage.