Exploring the Caffeine-Induced Teratogenicity on Neurodevelopment Using Early Chick Embryo

Abstract

Caffeine consumption is worldwide. It has been part of our diet for many centuries; indwelled in our foods, drinks, and medicines. It is often perceived as a “legal drug”, and though it is known to have detrimental effects on our health, more specifically, disrupt the normal fetal development following excessive maternal intake, much ambiguity still surrounds the precise mechanisms and consequences of caffeine-induced toxicity. Here, we employed early chick embryos as a developmental model to assess the effects of caffeine on the development of the fetal nervous system. We found that administration of caffeine led to defective neural tube closures and expression of several abnormal morphological phenotypes, which included thickening of the cephalic mesenchymal tissues and scattering of somites. Immunocytochemistry of caffeine-treated embryos using neural crest cell markers also demonstrated uncharacteristic features; HNK1 labeled migratory crest cells exhibited an incontinuous dorsal-ventral migration trajectory, though Pax7 positive cells of the caffeine-treated groups were comparatively similar to the control. Furthermore, the number of neurons expressing neurofilament and the degree of neuronal branching were both significantly reduced following caffeine administration. The extent of these effects was dose-dependent. In conclusion, caffeine exposure can result in malformations of the neural tube and induce other teratogenic effects on neurodevelopment, although the exact mechanism of these effects requires further investigation.

A New Oxidative Stress Model, 2,2-Azobis(2-Amidinopropane) Dihydrochloride Induces Cardiovascular Damages in Chicken Embryo

“…The fertilized eggs were incubated in a humidified incubator (Yiheng Instruments, Shanghai, China) set at 38°C and 70% humidity, until the chick embryos research the desired Hamburger-Hamilton (HH) stage of development [22], [23]. Before experiment, the air chamber of eggs was marked and live embryos were selected under an egg candler.…”

“…They were then dehydrated, embedded in paraffin wax and serially sliced at mid-ventricular level at 5 µm. For histology, the sections of coronal plane were de-waxed in xylene, rehydrated and stained with hematoxylin and eosin (H&E) dye [22]. The sections were photographed using a fluorescent microscope (Olympus IX50) with the NIS-Elements F3.2 software package.…”

Prenatal Caffeine Exposure and Child IQ at Age 5.5 Years: The EDEN Mother-Child Cohort

“…Caffeine administered in large amounts has been associated with teratogenic effects (i.e. neural tube, eye, cleft, cardiovascular and angiogenesis malformations) (1)(2)(3)(4)(5). Prenatal caffeine exposure can also lead to postnatal cognitive and behavioral changes in grown-up rodent offspring.…”

Investigating the effect of excess caffeine exposure on placental angiogenesis using chicken ’functional‘ placental blood vessel network

“…In addition, early chick embryos are susceptible to external factors making them excellent models for studying the effects of drugs as we have previously reported (Kucera and Burnand, 1987;Ma et al, 2012).…”