Anomalous costochondral cartilage in fetal anencephaly

Anencephaly is a human fetal malformation with absence of brain and calvari um superior to the orbits. The consequent absence of hypothalamus provides a unique model for studying human development, and therefore skeletal growt h, in the absence of hypothalamic hormones and their regulatory functions. To assess the influence of hypothalamic insufficiency on cartilage developm ent, we studied costochondral cartilage sections from eight anencephalic fe tuses (18-22 weeks old) and seven controls (16-22 weeks old) with pathologi es not directly related to skeletal growth. We found a previously undescrib ed anomalous organization of the cartilage in the anencephalic. The prolife rative chondrocytes showed a disordered appearance with an increased prolif erative zonal length (156 +/- 28 mu m in anencephalic fetuses vs. 103 +/- 1 4 mu m in controls, p = 0.006) and a concomitant decrease in the maturing p ortion, where cells form ordered isogenic groups (58 +/- 13 mu m in anencep halic fetuses vs. 93 +/- 19 mu m in controls, p = 0.003). In addition, cell density was significantly decreased in the proliferating and maturing zone s in the anencephalic cases (84 +/- 21 vs. 130 +/- 21 cells/40 mu m(2) in p roliferating zone; 53 +/- 8 vs. 94 +/- 8 in maturing portion, p < 0.005). T hese alterations in the developing cartilage of the anencephalic may contri bute to the observed growth retardation in these fetuses and reflect modifi cations in pituitary hormones and growth factors resulting from reduction i n hypothalamopituitary function.