Effects of Recombinant Murine Interferon-{gamma} on Pregnant Mice and Their Fetuses

Effects of Recombinant Murine Interferon- on Pregnant Mice andTheir Fetuses. KATO, I., KIMURA, S., FURUHASHI, T., NAKAYOSHI,H., TAKAYAMA, S., AND UENISHI, N. (1990). Fundam. Appl. Toxicol.14, 658–665. Recombinant murine interferon- (Rec-MuIFN-)was administered intramuscularly to C3H/HeNCrj mice on Days6-15 of gestation at dosage levels of 8 x 10⁵, 4 x 10⁶, and2 x 10⁷ u/kg/day. Dams were killed for examination of fetuseson Day 18 of gestation. Pregnant females that received 2 x 10⁷u/kg/day of Rec-MuIFN- showed uterine bleeding on Days 10–15of gestation and could not maintain their pregnancy. These damsdied on Days 13–17orwerekilled/ieWrem/sonDays 10–15for examination, and therefore no fetal data were availablefor this group. In the 2 x 10⁷ u/kg/day group, the mean absoluteweights of the lung and spleen increased and the mean absoluteweight of the liver, red blood cells (RBC), hematocrit, andhemoglobin decreased significantly. Surviving dams in the 8x 10³ and 4 x 10⁶ u/kg/day groups showed significant increasesin the mean absolute weights of the lung, liver, kidneys, andspleen and a decrease in platelet count. Significant increasesin the weights of the heart and ovaries and decreases in RBC,hematocrit, and hemoglobin were observed in the 4 x 10⁶ u/kg/daygroup. Histopathological examination revealed increased extramedullaryhema-topoiesis in the spleen of the 4 x 10⁶ and 2 x 10⁷ u/kg/daygroups. Fetuses showed no external, visceral, or skeletal malformationsand variations caused by the administration of Rec-MuIFN-7 inany of the treated groups. Although a slight but statisticallysignificant decrease in fetal body weight and a delay in ossificationwere seen in fetuses in the 4 x 10⁷ u/kg/day group, these findingswere considered to be the result of maternal toxicity and notfetal toxicity. No fetal effects were observed i n the 8 x 10⁵u/kg/day group.