Warfarin-Induced Reproductive Toxicity in Male Mice

Document Type : Original Article

Authors

1 Department of Pesticide Chemistry, Faculty of Agriculture, Alexandria University, Egypt

2 Central Laboratory for Food and Feed, Agriculture Research Center, Alexandria University, Egypt

3 Department of Histology, Faculty of Medicine, University of Alexandria, Egypt

Abstract

The reproductive toxicity of the rodenticide warfarin was studied in male mice. Adult male mice were treated by gavage with warfarin at doses of 0.01, 0.05, and 0.1 mg/kg/day for 4 weeks before mating with untreated females. Hematological parameters were determined for all the treated groups. Clinical signs of toxicity were observed at dose level of 0.1 mg/kg/day. Significant dose-related decreases in male hematocrit, hemoglobin content, and red blood cell counts were observed in all the treated groups. White blood cell counts were increased in all the treatments. Prothrombin time, total hemoglobin per cell [MCH], and mean cell volume [MCV] were significantly increased. Hemoglobin density per cell was decreased. Warfarin treatment was associated with a decreased number of live fetuses, and an increased number of dead fetuses at 0.1 mg/kg/day. The percent morphologically normal spermatozoa were unaffected in all dose groups; however, sperm motility and count were decreased in all the treatments. Dose related histological changes, including widening of the interstitial spaces, hemorrhage between the muscle fibers in the cardiac muscle, and extensive vacuolation in hepatocytes were observed. The current study demonstrated adverse effects of male warfarin exposure on pregnancy outcome with effects on sperm parameters at 0.1 mg/kg/day.

Keywords