Histostereological Teratogenic Effects of Prenatal Exposure to Carbamazepine on the Fetal Brain of Albino Rats (Rattus Norvegicus)

Abstract

The in-utero exposure to carbamazepine has been shown to perturb the normal morphogenesis of cortical and sub-cortical structurers of the fetal brain. However, the anatomical histostereological effects of prenatal exposure to carbamazepine when exposed at different gestation periods and at different doses is not well elucidated. The broad objective of this study was therefore to evaluate the histological teratogenic effects of prenatal exposure to varied doses of carbamazepine in different gestation periods. In conducting the study, a static group experimental study design was adopted. The animal experimentation was carried out at Small Animal Facility for Research and Innovation (SAFARI) animal house while tissue processing for histology and stereological analysis was done in the department of human anatomy. A Sample size of 30 albino rat dams (Rattus norvegicus) weighing between 200-250grams were used in the study as determined by use of the resource equation method. These 30 Albino rats were divided into two broad study groups of 3 rats control and 27 rats experimental. To evaluate the teratogenic histological effects of carbamazepine on differing doses, the 27 rats in the experimental group were further subdivided into three study groups of 9 rats as follows; (i) Low carbamazepine group[LCG-20.7mg/kg/bw] (ii) medium carbamazepine [MCG-72.3mg/kg/bw], (iii) High carbamazepine group[HCG-124mg/kg/bw].To further evaluate the teratogenic effects of carbamazepine on differing gestation periods, the 9 rats in each of the three dose categories were further sub-divided into three groups of 3 rats according to trimesters as follows; (i) Trimester I-(3rats); (ii) trimester II-(3rats) and (iii) trimester III-(3rats) respectively. The findings of the study showed that there is a statistical significant reduction (P<0.05) in cortical thickness of the cerebral and cerebellar cortices. It also caused a statistical reduction in cellular densities, disaggregation of corpus callosal fibres and ventricular hypertrophy. The most teratogenic effects were observed when exposed at trimester one and two across all the dose groups. In conclusion, carbamazepine is teratogenic to the developing fetal brains and its teratogenicity is time and dose dependent. The study recommends that carbamazepine should not be used during pregnancy and particularly during 1st and 2nd trimesters.