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

Objective: 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. Design: Differences in spontaneous tubal contractions and cellular distribution of t-ICC in isthmus were evaluated in response to MTX. Setting: Medical school research laboratory. Animal(s): Twenty nonpregnant female New Zealand albino rabbits in estrus stage were divided equally into four groups. Intervention(s): 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. Result(s): 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. Conclusion(s): 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. [Copyright &y& Elsevier]