Methotrexate enhances oxidative stress, apoptosis, and ultrastructural alterations in the placenta of rat. (2nd November 2022)

• Record Type: Journal Article
• Authors: Shalaby, Amany Mohamed; Albakoush, Khalid Mohammed Mohammed; Alabiad, Mohamed Ali; Alorini, Mohammed; Jaber, Fatima A.; Elkholy, Mahmoud Ramadan; Tawfeek, Shereen Elsayed
• Is Part Of: Ultrastructural pathology. Volume 46:Number 6(2022)
• Page Start: 531
• Page End: 541
• Publication Date: 2022-11-02
• Subjects: Caspase-3 -- electron microscopy -- methotrexate -- placenta -- VEGF; Pathology, Cellular -- Periodicals; Ultrastructure (Biology) -- Periodicals; Diagnosis, Electron microscopic -- Periodicals; Microscopy, Electron; Pathology; 616.07582
• DOI: 10.1080/01913123.2022.2154877
• Languages: English
• ISSNs: 0191-3123

Abstract

ABSTRACT: 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.