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Related Concept Videos

Teratogenicity01:07

Teratogenicity

The ability of a drug to produce structural deformations and functional abnormalities in the developing embryo or the fetus is called teratogenicity, and the drug producing this effect is known as a teratogen. Teratogenic effects include stillbirth, miscarriage, intrauterine growth restriction, and neurocognitive delay. A teratogen may affect the embryo at different stages of development, which is important in determining the type and extent of the damage. During blastocyst formation, the early...

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Updated: May 13, 2026

Comprehensive Evaluation of the Effectiveness and Safety of Placenta-Targeted Drug Delivery Using Three Complementary Methods
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Effect of methotrexate on rat placenta development.

Jing Sun1, Akihiko Sugiyama, Syouta Inoue

  • 1United Graduate School of Veterinary Science, Yamaguchi University, 1677-1 Yoshida, Yamaguchi, Yamaguchi 753-8515, Japan.

Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Fur Toxikologische Pathologie
|March 23, 2013
PubMed
Summary
This summary is machine-generated.

Methotrexate exposure during early gestation (GDs 11-12) significantly impacts rat placenta development, causing basal zone thinning and reduced fetal weight. Later exposure (GDs 13-14) shows less severe placental effects.

Keywords:
ApoptosisBasal zone hypoplasiaMethotrexatePlacentaRat

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Area of Science:

  • Reproductive toxicology
  • Developmental biology
  • Histopathology

Background:

  • Methotrexate is a chemotherapy agent with known teratogenic effects.
  • Understanding the specific placental vulnerabilities to methotrexate during different gestational periods is crucial for risk assessment.

Purpose of the Study:

  • To investigate the histopathological changes in rat placentas following methotrexate administration at different gestational stages.
  • To determine the sensitivity of placental zones to methotrexate exposure during critical developmental windows.

Main Methods:

  • Rats were administered methotrexate (0.2mg/kg/day) on gestation days (GDs) 11-12 or GDs 13-14.
  • Placentas were collected on GDs 13, 15, 17, and 21 for histopathological examination.
  • Fetal weight, mortality, and placental weight were assessed. Immunohistochemistry for Phospho-Histone H3 and TUNEL assays were performed.

Main Results:

  • Early methotrexate exposure (GDs 11-12) led to significant fetal weight reduction, increased fetal mortality, and placental weight decrease.
  • Histopathology revealed severe basal zone thinning and labyrinth zone reduction in early-exposed placentas, with decreased glycogen cells and altered cell proliferation/apoptosis (reduced PHH3, increased TUNEL).
  • Later exposure (GDs 13-14) resulted in minimal placental changes, primarily labyrinth zone thinning on GD 17.

Conclusions:

  • The placental basal and labyrinth zones are more sensitive to methotrexate during early gestation (GDs 11-12) compared to later stages (GDs 13-14).
  • Methotrexate exerts a stronger detrimental effect on the basal zone's cellular components than on the labyrinth zone.
  • These findings highlight critical windows of placental vulnerability to teratogenic agents like methotrexate.