Deleterious effects of prenatal prednisolone exposure upon morphological and behavioral development of mice.

The influence of prenatal exposure to the synthetic glucocorticoid prednisolone (PRED) was examined in female offspring of mice administered the drug on Days 13-18 of pregnancy. The offspring weighed significantly less than control animals at birth and weaning. Animals born of mothers given the highest dosage of the drug (400 microgram) weighed less than controls in adulthood. Fetal exposure to PRED also resulted in morphological masculinization as evidenced by an increase in anogenital distance. In addition to its marked influence, prenatal PRED exposure retarded the attainment of the developmental milestones of eye opening, lifting, walking, and gripping. The effect of PRED upon the fetus is relatively rapid in that a reduction of fetal weight was observed in 13-day-old conceptae 7.5 hr following a maternal injection of PRED. The administration of an antiestrogenic compound (MER-25) concurrently with PRED prevented the reduction in birth weight, thereby suggesting that PRED acts, in part, by its known attenuation of fetoneonatal estrogen-binding protein. And finally, fetal exposure to PRED had virtually no effect upon reproductive competence as assessed by proportion of successful pregnancies, lactation performance, and postpartum fighting behavior. It is concluded that prenatal exposure to PRED markedly affects somatic and muscular/motor development and it may be worthwhile to examine the influence of the drug upon levels of gonadal hormones in an attempt to elucidate the mechanism through which its effects are produced.