Light and electron microscope examination of the effects of methotrexate on the endosalpinx

Eur J Obstet Gynecol Reprod Biol. 2005 May 1;120(1):96-103. doi: 10.1016/j.ejogrb.2004.08.014.


Objective: To examine the effects of increasing doses of methotrexate (Mtx) on the fallopian tubes.

Study design: The study was carried out on 24 female rats (Albino Wistar type, 250-300 g). The rats were randomly divided into four groups of six. Different doses of Mtx were given to the rats by i.p. injection: 1mg/kg to those in group 1, 5mg/kg in group 2 and 10 mg/kg in group 3. Rats in group 4 received injections of physiological serum only and were treated as the control group. Ten days after the injection, the fallopian tubes of the rats were removed for examination separately by light and electron microscopy (EM) for comparison.

Results: Light microscopy showed that in group 1 the surface epithelial cells were normal and the lamina propria was infiltrated by numerous inflammatory cells with a prevalence of polymorphonuclear leucocytes. Findings in groups 2 and 3 were similar: the lamina propria was infiltrated with granulocytes in one specimen from each of the two groups, and granulocytes were also observed among epithelial cells. In the control group all surface structures were found to be in a normal condition. Electron microscopy showed cilial loss in the epithelial cells and central crystolysis in mitochondria in all group 1 specimens. Findings in groups 2 and 3 were similar. The cytoplasm of the epithelial cells seemed to be dense, there was prominent crystolysis (crystalloid formation) in the mitochondria, and vacuolisation (vacuole formation) in the cytoplasm seemed to be augmented. Cilial loss was prominent, and the basal membrane was irregular. Epithelial cell nuclei were in disorder. Lipid granules were observed extensively in epithelial cells. Eosinophils seemed to be dominant in connective tissues below the epithelium. In all control group specimens the epithelium seemed to be normal with all organelles in place; the condition of intercellular junctions, ciliated epithelium and all mitochondria also seemed to be normal, and the basal membrane was observed to be in order.

Conclusion: In view of these findings, we conclude that the ultrastructural derangements resulting from administration of Mtx in doses in excess of 1mg/kg can cause a reduction in the surface epithelium's ability to make rhythmic lashing movements and can impair the patency of the fallopian tubes. All these disturbances could be involved to some degree in the causation of infertility and recurrent ectopic pregnancy. Therefore, the dosage of Mtx should be limited to use of the lowest effective dose to avoid these adverse effects.

MeSH terms

  • Animals
  • Cell Nucleus / drug effects
  • Cell Nucleus / ultrastructure
  • Cilia / drug effects
  • Cilia / ultrastructure
  • Cytoplasm / drug effects
  • Cytoplasm / ultrastructure
  • Dose-Response Relationship, Drug
  • Epithelial Cells / drug effects
  • Epithelial Cells / ultrastructure
  • Fallopian Tubes / drug effects*
  • Fallopian Tubes / ultrastructure
  • Female
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects*
  • Microscopy, Electron
  • Rats
  • Rats, Wistar


  • Methotrexate