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

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.

KEYWORDS:

• Caspase-3
• electron microscopy
• methotrexate
• placenta
• VEGF

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data Availability

On reasonable request from the corresponding author.

Author Contributions

All authors contributed to the study’s conception and design. Material preparation, data collection, and analysis were performed by dr [Amany Mohamed Shalaby], [Mohamed Ali Alabiad], [Khalid Mohammed Mohammed Albakoush], [Mohammed Alorini], [Mahmoud Ramadan Elkholy], and [Shereen Elsayed Tawfeek]. The first manuscript draft was written by [dr Amany Mohamed Shalaby], and all authors commented on previous versions. All authors read and approved the final manuscript.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.