Inhibitory effects of methotrexate on spontaneous motility and cajal-like type of tubal interstitial cells in rabbit oviduct

Methotrexate toxicity causes diminished tubal smooth muscle contractility, probably due to decreased population of t-ICC, which may be new potential targets for a variety of dysfunctional tubal motility diseases.

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Xiao-Jun Yang, Ph.D., Wei Wei, M.D., Jing Zhao, M.D., Fei-Yun Zheng, M.D.

Vol 98, Issue 1 , Pages 215-221



To study the adverse biomechanical effects of methotrexate (MTX) on spontaneous tubal motility and on a widely distributed Cajal-like type of tubal interstitial cells (t-ICC) in rabbits. In our previous study, MTX was confirmed to cause acute endosalpingitis, and ultrastructural and steroid receptor damage in rat's endosalpinx in a dose-dependent manner.


Differences in spontaneous tubal contractions and cellular distribution of t-ICC in isthmus were evaluated in response to MTX.


Medical school research laboratory.


Twenty nonpregnant female New Zealand albino rabbits in estrus stage were divided equally into four groups.


Rabbits received IM MTX (1, 5, 10 mg/kg body weight) and controls received physiological saline.

Main Outcome Measure(s):

On day 7, in vitro motility studies measuring spontaneous tubal contractions were performed, and cellular distribution of t-ICC was determined by immunohistochemistry.


Methotrexate produced a concentration-dependent inhibition of spontaneous isthmus contractions (frequency in 5, 10 mg/kg groups, and amplitude in 1, 5, 10 mg/kg MTX groups). It decreased significantly compared with the control group. Meanwhile, MTX at 5, 10 mg/kg decreased the population of c-kit immunoreactive t-ICC significantly.


The decreased t-ICC may contribute to the diminished tubal smooth muscle contractility caused by MTX as observed. Tubal interstitial cells might be new potential targets for a variety of dysfunctional tubal motility diseases.

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Fertility and Sterility

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