Cyclophosphamide in the male rat: behavioral effects in the adult offspring

Cyclophosphamide in a daily dose of 10 mg/kg was injected intraperitoneally in male Wistar rats for 15 days. Two rats each time were killed for testis examination at regular intervals within 100 days following treatment (over 2 spermatogenetic cycles). One hundred days after the end of the treatment, the other rats, whose spermatogenesis had recovered in the meantime, were mated with 3-month-old females. Offspring were evaluated in regard to the mean number per litter, sex ratio, frequency of gross external malformations, growth pattern, mortality in the first 4 months of life and reproductive ability at 6 months of age. Offspring behavior was also examined between 10 and 14 weeks of age. They were evaluated for spontaneous activity and emotionality with an open field test and for learning ability with an avoidance conditioning test. Cyclophosphamide induced a significant decrease in the number of primary spermatocytes and spermatozoa. Only learning ability was altered in the offspring from the treated males, for the animals which succeeded in the avoidance conditioning test did not learn as rapidly as the controls. However, the difference was significant only in the males. Behavioral abnormalities and the possible genetic factors involved are related to the particular concept of 'physioteratogenesis'.