Prenatal isotretinoin exposure reduces the neuronal population of hippocampus in rats

Isotretinoin is a drug used in the treatment of acne. Teratogenic effects of isotretinoin are well known. It is causes craniofacial abnormalities like cleft palate in animal model studies. There are very few studies focusing on its effect on the developing brain specially hippocampus concerned with memory. In the present study we investigate teratogenic effect on neuronal population of the hippocampus during postnatal development. Pregnant Wistar rats were exposed to either 8 or 16mg/kg dose of body weight of isotretinoin during early or mid-gestation of pregnancy. Pups were sacrificed at postnatal day 7 or day 21, brains were removed and processed for histological studies. Coronal sections o brain were taken and stained with cresyl violet and viable neurons were counted for 250 μm length in different regions of the hippocampus. At postnatal day 7neurons belonging to CA1 region of the hippocampus was severely affected at both the doses tested and also in early & mid-gestation treatment regime. At postnatal day 21, neurons of the CA2 & CA1 regions were severely affected. It is also observed that mid-gestational effect had more severe effect compared to early gestational treatment. This study clearly demonstrates the teratogenic effect of isotretinoin on hippocampal neuronal population of developing brain. Care must be taken while prescribing this drug to women of reproductive age.