“Wavy ribs” A reversible pathologic finding in rat fetuses

A literature of 74 scientific papers addressing the occurrence of “wavy ribs” in fetuses of small rodents has been collected with the support of a computer-assisted search on MEDLINE, TOXLINE, BIOSIS and EXCERPTA MEDICA systems (1982-1993) and has been critically examined. Numerous compounds of a large variation in chemical structure and biological activity, if given to pregnant rats during the later period of organogenesis, are known to cause “wavy ribs” in their fetuses, a reversible pathologic finding which is rarely observed in untreated controls. According to literature, causative factors, like delayed development of alkaline phosphatase, decreased fetal protein, dietary contents, maternal toxicity, renal loop diuretics, myometrial constriction, endocrine disturbances and beta-adrenoceptor stimulation or blocking have been observed and discussed, but, a general explanation for the lesions is still missing. Therefore, the following hypothesis may be added: the high doses used in reproductive toxicology may induce maternal and placental circulatory disturbances leading to reductions in fetal serum proteins, with delayed development of osteoblast progenitors and low fetal serum alkaline phosphatase in the day 17–20 fetus. Normalization of the neonate's homeostasis (serum protein) leads to enhanced ossification and concomitant bone repair until weaning.