Embryonic and postnatal injections of bromodeoxyuridine produce age-dependent morphological and behavioral abnormalities

The mitotic marker 5-bromodeoxyuridine (BrdU) was injected twice daily (60 mg/kg) into pregnant hooded rats on one of embryonic days (E) 11, 12, 13, 1 5, 17, or 21, or into rat pups on postnatal day (P) 10. The principal findi ngs were the following: (1) BrdU exposure on E11 produces profound effects on body morphology, and animals must be fed a special diet because of chron ic tooth abnormalities; (2) BrdU exposure at E17 or earlier produces a chan ge in coat spotting pattern, the precise pattern varying with age; (3) BrdU exposure on E15 or earlier produces a reduction in both brain and body wei ght; (4) BrdU exposure on E17 or earlier reduces cortical thickness; (5) Br dU exposure on E11-E13 and at P10 reduces cerebellar size relative to cereb ral size; (6) spatial learning is significantly affected after injections o f BrdU at E11-E17, but the largest effect is on E17; (7) the deficit in spa tial learning may be related in part to a reduction in visual acuity; and ( 8) skilled forelimb ability is most disrupted after BrdU exposure at E15 bu t is also impaired after injections on E13 or earlier. BrdU thus has terato logical effects on body, brain, and behavior that vary with the development al age of the fetus or infant.