Life sciences · 2025
Effects of antiseizure drugs zonisamide, oxcarbazepine, clobazam, and lacosamide on FOXO1, LIF, and E-cadherin- mediated molecules in rat embryo implantation.
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Durgut Betül Diler, Kart Pınar Özkan, Sarsmaz Hayrunnisa Yeşil, Gürgen Seren Gülşen, Cansu Ali
Аннотация
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.
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.