Bis-diamine administration during pregnancy induces developmental and reproductive toxicities in rats.

Abstract

Bis-diamine was developed as amebicidal and male contraceptive agents; however, it is also reported to induce characteristic congenital heart defects especially in the cardiac conotruncal area of rats. Because of its characteristic congenital heart defects, bis-diamine-induced animal models can be used for studying congenital heart defects. However, comprehensive toxicological information regarding bis-diamine-induced congenital heart defects in this animal model is not available. In this study, we investigated and characterized an animal model for bis-diamine-induced congenital heart defects. A single dose of 200-mg bis-diamine was administered by oral gavage to pregnant rats on gestation day 10, and then observed the representative toxicological endpoints for general systemic health of pregnant rats, embryo-fetal development, and parturition. Characteristic congenital heart defects and other birth defects similar to DiGeorge syndrome were observed in bis-diamine-administered pregnant rats. In addition, developmental and reproductive toxicity findings, including increased postimplantation loss, decreased fetal weight, increased perinatal death, and increased gestation period, were observed in bis-diamine-administered pregnant rats. In particular, these developmental and reproductive toxicities were observed without maternal toxicity findings. These results will be useful to use this animal model for further studies in congenital heart defects, cardiovascular defects, and understanding their mechanisms.