Effects of antiseizure drugs zonisamide, oxcarbazepine, clobazam, and lacosamide on FOXO1, LIF, and E-cadherin- mediated molecules in rat embryo implantation.

AIMS: This study aimed to evaluate the effects of commonly used antiseizure drugs-lacosamide (LCM), zonisamide (ZNS), oxcarbazepine (OXC), and clobazam (CLB)-on uterine implantation in a non-epileptic juvenile-to-adult rat model.

MATERIALS AND

METHODS

Fifty female Wistar rats were divided into five groups: control, ZNS (100 mg/kg/day), LCM (30 mg/kg/day), CLB (12.5 mg/kg/day), and OXC (100 mg/kg/day). Drugs were administered orally for 90 days. Mating was synchronized with estrous cycles, and implantation sites were assessed histologically using hematoxylin-eosin staining. Immunohistochemistry was performed to evaluate expression of leukemia inhibitory factor (LIF), E-cadherin, and transcription factor Forkhead Box O1 (FOXO1), quantified by H-score analysis.

KEY FINDINGS: Expression levels of LIF, E-cadherin, and FOXO1 were significantly lower in all treatment groups compared to controls (p < 0.001). Tukey's post hoc analysis revealed significant differences in LIF and E-cadherin among most groups (p < 0.05). No significant differences in FOXO1 expression were observed between ZNS vs. CLB (p = 0.152) or ZNS vs. LCM (p = 0.070), while all other comparisons were significant (p < 0.05). The most pronounced reduction in implantation markers was found in the LCM group.

SIGNIFICANCE: These results suggest that long-term administration of ZNS, OXC, CLB, and LCM may impair implantation by altering key molecular markers. The findings highlight potential reproductive risks associated with chronic antiepileptic drug exposure during adolescence.