Methotrexate enhances oxidative stress, apoptosis, and ultrastructural alterations in the placenta of rat

Autor: Amany Mohamed Shalaby, Khalid Mohammed Mohammed Albakoush, Mohamed Ali Alabiad, Mohammed Alorini, Fatima A. Jaber, Mahmoud Ramadan Elkholy, Shereen Elsayed Tawfeek
Rok vydání: 2022
Předmět:
Zdroj: Ultrastructural Pathology. 46:531-541
ISSN: 1521-0758
0191-3123
DOI: 10.1080/01913123.2022.2154877
Popis: The chemotherapeutic drug methotrexate (MTX) is utilized to treat various malignancies. MTX exposure during pregnancy causes miscarriages, abnormalities in newborns, and developmental delays. The current study examined the placenta's sequential histopathological alterations following exposure to the MTX in pregnant rats. Twenty-four pregnant rats were assigned into; the control group and MTX group (0.2 mg/kg). MTX was given intraperitoneally on gestational days 11-12. Oxidative stress parameters were measured in placental homogenates. The placental specimens were evaluated by light, immunohistochemical (caspase-3 and vascular endothelial growth factor (VEGF)), and electron microscopic study. Malondialdehyde levels were significantly elevated by MTX, whereas glutathione peroxidase and superoxide dismutase levels were significantly reduced. The MTX group showed a marked reduction in the thickness of both the basal and labyrinth zones. Degeneration of the labyrinth zone was demonstrated. Also, giant trophoblast cells and the spongiotrophoblasts of the basal zone showed vacuolations with dark nuclei. Up-regulation of caspase-3 and down-regulation of VEGF immunoexpression were demonstrated. Ultrastructurally, disintegration of the interhemal membrane, spongiotrophoblasts with vacuolated cytoplasm and small condensed nuclei, and the giant trophoblasts with irregular nuclear outlines and vacuolated cytoplasm were demonstrated. In conclusion, MTX has profoundly altered the structure of the placenta.
Databáze: OpenAIRE
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