title: Caffeine interferes embryonic development through over-stimulating serotonergic system in chicken embryo.
abstract: 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 ED(50) value of caffeine toxicity was 27.3 μmol/egg in chicken embryo. Administration of caffeine, with lower dosage than ED(50) (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.
authors.affiliation: Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou 510632, China. so_didi@163.com
authors.forename: Xiao-Di
authors.initials: XD
authors.lastname: Li
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: He
authors.forename: Yang
authors.initials: Y
authors.lastname: Qin
authors.forename: Bun
authors.initials: B
authors.lastname: Tsoi
authors.forename: Yi-Fang
authors.initials: YF
authors.lastname: Li
authors.forename: Zheng-Lai
authors.initials: ZL
authors.lastname: Ma
authors.forename: Xuesong
authors.initials: X
authors.lastname: Yang
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kurihara
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002642:Chick Embryo; D002645:Chickens; D002851:Chromatography, High Pressure Liquid; D047108:Embryonic Development / Q000187:drug effects*; D054259:Neural Tube / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012701:Serotonin / Q000502:physiology*; D013056:Spectrophotometry, Ultraviolet; D014365:Tryptophan Hydroxylase / Q000096:biosynthesis / Q000235:genetics
chemical_list: D015306:Biogenic Monoamines; D000697:Central Nervous System Stimulants; D018377:Neurotransmitter Agents; D012333:RNA, Messenger; D012701:Serotonin; D002110:Caffeine; D014365:Tryptophan Hydroxylase