Gross-structural defects in rats after acyclovir application on day 10 of gestation

Abstract

Following three s.c. injections of acyclovir (100 mg acyclovir/kg) into rats on day 10 of pregnancy 19 litters were evaluated on day 21 of gestation and the effects were compared to the results obtained from controls (nine litters) which received the vehicle (0.1 N NaOH) only. The following results were obtained (treated group versus control group): 1) Implantations/litter: 11.2±1.3 versus 10.2±1.1; 2) resorptions/implantations: 27.7% versus 2.2%; 3) number of viable fetuses evaluated: 154 versus 90; 4) fetuses with anomalies of the skull: 78% versus 12%; 5) fetuses with anomalies of the vertebral column: 38% versus 13%; 6) gross-structural anomalies predominantly affected the skull and tail. The most frequently registered defects were: os tympanicum (smaller): 23%, os tympanicum (missing): 23%; missing tail: 7%; protruding tongue (15%); none of these defects were seen in the control fetuses. Postnatally we observed a high mortality rate among the offspring. From a total of 85 newborn (nine litters) we obtained 73 viable offspring (9.1±3.4); 81% of them had tail alterations. In the control group of eight litters (9.4±2.3) no tail alterations occurred. On day 21 postnatally 40 viable offspring were alive (mortality rate: 38.8%). Nearly all of these animals had visible alterations at multiple sites of their bodies; most frequently observed were: tail impairment, closed eyes, dragging hind-limbs, and urogenital alterations (e.g. testicular atrophy). These studies show for the first time that prenatal treatment with acyclovir induces gross-structural defects which persist postnatally. With the usually applied precautions during therapeutic use in pregnant women, the teratogenic potency of acyclovir seems to be small; however, acyclovir does have a teratogenic potential.