Anomalous Costochondral Cartilage in Fetal Anencephaly

Anencephaly is a human fetal malformation with absence of brain and calvarium superior to the orbits. The consequent absence of hypothalamus provides a unique model for studying human development, and therefore skeletal growth, in the absence of hypothalamic hormones and their regulatory functions. To assess the influence of hypothalamic insufficiency on cartilage development, we studied costochondral cartilage sections from eight anencephalic fetuses (18–22 weeks old) and seven controls (16–22 weeks old) with pathologies not directly related to skeletal growth. We found a previously undescribed anomalous organization of the cartilage in the anencephalic. The proliferative chondrocytes showed a disordered appearance with an increased proliferative zonal length (156 ± 28 μm in anencephalic fetuses vs. 103 ± 14 μm in controls, p = 0.006) and a concomitant decrease in the maturing portion, where cells form ordered isogenic groups (58 ± 13 μm in anencephalic fetuses vs. 93 ± 19 μm in controls, p = 0.003). In addition, cell density was significantly decreased in the proliferating and maturing zones in the anencephalic cases (84 ±21 vs. 130 ± 21 cells/40 μm² in proliferating zone; 53 ± 8 vs. 94 ± 8 in maturing portion, p < 0.005). These alterations in the developing cartilage of the anencephalic may contribute to the observed growth retardation in these fetuses and reflect modifications in pituitary hormones and growth factors resulting from reduction in hypothalamopituitary function.