Impairment of bone growth of wistar rat fetuses of diabetic and hypercholesterolemic mothers

Patients with either diabetes or hypercholesterolemia develop atherosclerosis and impair healing of bone. In the present work we illustrated their role in limb ischemia during bone cells differentiation of Wistar rat fetuses. Pregnant Wistar rats (n = 20 each) were arranged in three groups: control, diabetic or hypercholesterolemic. Diabetes was induced at the fifth day of gestation using streptozotocin, and hypercholesterolemia was carried by feeding virgin rats a diet containing 3% cholesterol for 6 wks prior to the onset of conception. At 13, 15, 17, and 19 d prenatal, pregnant rats were sacrificed, dissected, and fetuses were removed. Hind limbs were separated and subjected to histological and transmission electron microscopic examination, ossification, total calcium content of fetuses, isoenzymes alkaline and acid phosphatase and lactic dehydrogenase electrophoresis and DNA damage. Fetuses of diabetic or hypercholesterolemic mothers exhibited delayed histo-cytological differentiation of chondrocytes, and decreased periosteal ossification. Alkaline and acid phosphatase as well as lactic dehydrogenase isoenzymes showed altered diffusion rate and intensities of their bands reflecting their activities in both diseases comparing with the control. Assessments of bone calcium contents revealed marked reduction. Genomic expression of the degree of laddering (total DNA fragmented) or single-cell gel electrophoresis was found to be increased in cartilage and bone cells of fetuses of diabetic or hypercholesterolemic mothers. The authors concluded that both diseases had a selective, dramatic effect during fetus development in this model by retarding the histo- and cytological differentiation during limb bone growth. Both diseases increased the average cell death in skeletal elements and blood vessels as a consequence of altered alkaline and acid phosphatases and lactic dehydrogenase isoenzymes in accordance with DNA damage.