Effects of prenatal PPAR-γ agonist rosiglitazone exposure on rat hippocampus development in a time-dependent manner: A stereological and histopathological study

Abstract

Rosiglitazone is in the thiazolidinedione class of drugs used in the treatment of type 2 diabetes mellitus. It works as an insulin sensitizer by binding to the peroxisome proliferator–activated receptor gamma. We investigated the effects of prenatally administered rosiglitazone on pyramidal cell numbers and morphologies in the hippocampus at postnatal period using histochemical and stereological techniques, congenital morphological properties and the number of offspring in rats. Eighteen female rats were grouped into control (C), low-dose rosiglitazone (LDR) and high-dose rosiglitazone (HDR). LDR pregnant rats received 2 mg/kg/day of rosiglitazone via oral gavage during the first 16 days of the pregnancy. HDR rats received 5 mg/kg/day. The infants were grouped into newborn (NB), 4 week (4 W) and 12 week (12 W). A side from histopathologic and congenital assessments, stereological analyses were performed using the optical fractionator method. Congenital anomaly was not detected in any of the rosiglitazone treatment groups, and their number of offspring was similar to that of the C group. Stereological counts revealed a significant reduction in the number of hippocampal pyramidal cells in the C and LDR groups but not in the HDR group until birth to 12th week. When NB groups were compared, the number of pyramidal cells in the HDRNB group was less than those in the LDRNB and CNB groups. HDR affected apoptosis or the proliferation and maturation of progenitor cells to the pyramidal neuron during neurodevelopment in the hippocampus, whereas LDR did not adversely affect neuronal development and did not cause congenital anomalies.