Narotsky, MG; Hamby, BT; Best, DS; Kavlock, RJ
Prenatal exposure to boric acid (BA) has been shown to cause shortening or agenesis of the 13th rib, as well as reduced incidences of supernumerary ribs, in multiple laboratory species. We sought to more fully characterize the morphological changes in the axial skeleton caused by BA. Sprague-Dawley rats were treated by gavage with 500 mg/kg b.i.d. on gestation day (GD) 6, 7, 8, 9, 10, or 11 (GD 0 = plug day). Distilled water was used as the vehicle; animals received 10 ml/kg/dose. Progeny were delivered by cesarean section on GD 21 and were subsequently stained with alizarin red S and alcian blue for skeletal examination. Groups exposed on GD 6, 7, 8, and 11 were generally unaffected. Treatment on GD 9 or 10, however, resulted in dramatic, but strikingly different, alterations in the axial skeleton. In the GD-9 group, about 90% of the fetuses had only six cervical vertebrae; the deficient region was usually C3-C5, with C7 or C6 being affected less frequently. Only one fetus had a rib on C7, however, vertebra T1 (bearing a rib with a prominent costal cartilage) sometimes showed cervical characteristics as well as altered attachment of the costal cartilage to the sternum. Increased incidences of fetuses with 14 thoracic ribs were also seen in GD-9 exposed litters. In contrast, GD10 treatment caused agenesis of a thoracic and/or lumbar vertebra in over 60% of the fetuses. For 12-ribbed fetuses, vertebral morphology indicated that the deficient thoracic region was usually Tll, with the T3-10 and T12-13 regions being affected less frequently. The pattern of costal cartilage attachment to the sternum was also altered in this group, predominantly at the caudal end. The number of sternebrae, or the associated costal cartilage, did not necessarily correspond with the number of vertebrae in the morphologically-defined thoracic regions. Interestingly, both GD-9 and GD-10 exposed fetuses had reduced numbers of sternebrae. These findings demonstrate the critical periods for axial development in the rat, as well as BA's ability to induce homeotic shifts in this species.