Effects of Treatment with Clinically Relevant Valproate, Carbamazepine, Oxcarbazepine, Topiramate, Lamotrigine and Levetiracetam on Ovarian Folliculogenesis in Young Rats

To determine the effects of valproate (VPA), carbamazepine (CBZ), oxcarbazepine (OXC), topiramate (TPM), lamotrigine (LTG), and levetiracetam (LEV) on ovarian folliculogenesis in young rats. Forty-nine female Wistar rats, aged 21–24 days, were divided equally into 7 experimental groups. These were given tap water over 21-24 days (control group), 300mg/kg of VPA, 150mg/kg of CBZ, 150mg/kg of OXC, 100mg/kg of TPM, 10mg/kg of LTG, or 50mg/kg of LEV daily in 2 doses via oral gavage until the end of puberty. At the end of the study, the estrous cycle of each rat was monitored daily, and those rats in pro-estrus or di-estrus were sacrificed and the ovaries removed. Serial sections obtained from the ovaries were stained with hematoxylin and eosin, and the corpora lutea and follicles were enumerated. Apoptotic cells were detected using the TUNEL technique. Various serial sections were immunohistochemically stained with proliferating cell nuclear antigen (PCNA), growth differentiation factor (GDF)-9, caspase-3, caspase-9, transforming growth factor beta 1 (TGF-1), and epidermal growth factor (EGF), and evaluated and photographed under a light microscope. The number of corpora lutea was significantly increased in the VPA, CBZ, OXC, and LTG groups compared to the control group (p