Adverse prenatal neurotoxicity induced by administration of caffeine to pregnant rats.

Abstract

The effects of caffeine on the developing brain remain controversial; therefore, the present study examined the developmental profiles of nucleic acids, proteins, and monoaminergic metabolism in immature rat brain and their impact on brain development in fetuses exposed to caffeine throughout pregnancy. Thirty pregnant rats were divided into three groups ten rats each, treated orally via gavage tube with caffeine at a doses of 0, 75 or 120 mg/kg b.wt./day, from the 1st to the 19th day of gestation. At the end of the experimental period, rats were sacrificed; blood samples and fetal amniotic fluids were taken. The maternal serum and amniotic fluid concentrations of calcium, phosphorus and the total protein content were estimated. The uteri were removed, weighed and examined. Caffeine levels in the maternal serum and fetal brain were evaluated. Fetal brain samples were obtained for different biochemical analyses and histopathological examination. The results indicated that dams received caffeine at either75 or 120 mg/kg bwt did not produce any adverse effect on the number of implantation, live fetuses or pre- or post-implantation loss. However, a significant reduction of fetal body weight was apparent in both doses. Caffeine levels of maternal serum and fetal brain were elevated significantly with the increase of caffeine dosage. High dose treated dams exhibited significant reduction of serum total protein content and their fetuses exhibited significant decrease of nucleic acids, total protein contents and neuronal density of fetal brain. Caffeine ingestion by pregnant rats at two doses induced a significant decrease of norepeniphrine in fetal brain but there was a significant increase in dopamine level. Therefore, caffeine received by pregnant rats can induce alterations in the steady-state concentrations of some neurotransmitters. Also, it can interfere with neuronal proliferation in the fetal brain especially at the high dose resulting in abnormal cerebral development that could lead to postnatal neurobehavioral disturbances.