Tissue effects of methotrexate injected into the uterine horn of pregnant female rats

Methotrexate has been proposed as a treatment for unruptured extra-uterine pregnancy, but its effects on the tubal wall remain unknown. In order to analyse these effects, an experimental study was carried out on two groups of pregnant female rats, one receiving methotrexate (n = 8) and the other sodium chloride (n = 6). In both groups, a single intra-embryonic injection was performed in the uterine horn. The genital tract was prepared for histological examination. In all rats which received a single dose of methotrexate (5 mg per 100 g body weight) six days after mating and were killed nine days later, the labyrinthine part and the junctional zone of the placenta were necrotic at the site of the injection, with no embryonic development. The other parts of the genital tract were not visibly altered. In rats receiving sodium chloride and killed under the same conditions, necrosis of the placenta was observed at the site of injection in three animals. In the other three rats, a focal necrosis of the placenta was found, which was probably of mechanical origin. From this study, we conclude that methotrexate is efficient in killing normally implanted embryos and is, at least under light microscopy, non-toxic to the adjacent portions of the genital tract.