Effects of valproic acid, levetiracetam, carbamazepine, lamotrigine, and topiramate on LIF, E-cadherin, and FOXO1 mediator molecules in rat embryo implantation

Kart P. Ö., Yıldız N., GÜRGEN S. G., Sarsmaz H. Y., CANSU A.

Food and Chemical Toxicology, cilt.199, 2025 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 199
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1016/j.fct.2025.115352
  • Dergi Adı: Food and Chemical Toxicology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, PASCAL, Aqualine, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, Environment Index, Food Science & Technology Abstracts, Pollution Abstracts, Veterinary Science Database
  • Anahtar Kelimeler: Antiseizures medication, Embryo implantation, LIF, E-Cadherin, FOXO1
  • Manisa Celal Bayar Üniversitesi Adresli: Evet

Özet

Background: This study investigated the effects of valproic acid (VPA), levetiracetam (LEV), carbamazepine (CBZ), lamotrigine (LTG), and topiramate (TPM) on LIF, E-cadherin, and FOXO1 mediator molecules during implantation in rat embryos. Materials and methods: Sixty female rats were divided into six experimental groups, and the control solution and drugs were administered by gavage for 90 days. At the end of three months, implantation sites were obtained, and histological and immunohistochemical staining protocols were applied. Results: Embryonic trophectoderm cells were surrounded by inflammatory cells in the VPA group. Increased eosinophilic staining was seen in the primary decidual zone cells in the CBZ group, mast cells in the LTG group, and intense inflammatory cells in the TMP group. LIF staining in the VPA, CBZ, LTG, and TPM groups showed weak to moderate LIF expression (p < 0.001). In E-cadherin staining, the LTG group showed moderate and the TPM group showed weak immune reactions (p < 0.001). Embryonic cells and primary decidual zone cells in control, LEV, CBZ, and LTG groups showed weak to strong expression of FOXO1, while VPA and TPM groups showed no reaction (p < 0.001). Conclusions: In summary, antiseizure medication use had a negative effect on the expression of proteins that play key roles in embryo implantation in young non-epileptic rats to varying degrees.