Changes in the fetal tibial growth plate secondary to maternal zinc deficiency in the rat: A histological and histochemical study

Abstract

Zinc deficiency (ZD) is teratogenic in rats, and fetal skeletal defects are prominent. To elucidate further the effects of maternal ZD in the fetal skeleton, we performed a morphological and histochemical study of tibial growth plate (GP) in ZD rat fetuses. The histochemical study included the identification of calcium, of hydrolytic enzymes associated with the process of calcification, and of oxidative enzymes related to energy production and to the synthesis of proteoglycans. Pregnant Sprague-Dawley rats were fed (1) a control diet (76.4 micrograms Zn/g diet) ad libitum (group C), (2) a zinc-deficient diet (0 micrograms/g) ad libitum (group ZD), or (3) the control diet pair-fed to the ZD rats (group PF). On day 21 of gestation, laparotomies were performed, the fetuses were removed, and fetal tibiae obtained. Specimens were stained with hematoxylin-eosin (H&E) and Masson Trichrome and were processed for identification of alkaline phosphatase, adenosine triphosphatase, succinic dehydrogenase, NADH dehydrogenase, and calcium. The morphologic patterns found in ZD fetal tibiae indicated defects in various cell types implicated in bone metabolism. Staining for hydrolytic enzymes revealed alterations in the size and distribution of matrix vesicles and a weaker staining for ATPase in ZD fetuses. Staining for oxidative enzymes was overall more intense in ZD fetal tibiae. ZD fetuses also presented irregular and defective calcification. These findings indicate that severe maternal ZD in the rat results in structural and functional alterations in the GP of fetal bone, leading to a defective endochondral ossification.

Dietary zinc reduces osteoclast resorption activities and increases markers of osteoblast differentiation, matrix maturation, and mineralization in the long bones of growing rats

“…When pair-feeding was used, the effects of Zn deficiency on bone were attributed to reduced osteoblast modeling activity only [3,38] or in combination with reduced osteoclast numbers [7]. In the present study, stepwise increases in dietary Zn produced incremental differences in metaphyseal trabecularization, consistent with previous comparisons between severely deficient and adequate groups [1,[4][5][6][7]. Here, graded levels of dietary Zn ranged from severely deficient (2.5 μg/g) to adequate (30 μg/g), and normal growth was maintained by 7.5 μg Zn/g diet.…”

“…Later, O'Dell et al [2] (1957) also reported defective hypertrophic chondrocyte proliferation related to low dietary Zn, providing additional evidence for an osteogenic Zn requirement. Bone formation in Zn-deficient animals is characterized by retarded growth plate activity [3][4][5][6] and is associated with reduced cancellous and trabecular volume [3,7,8]. The biophysical consequences of these events include decreased longitudinal and radial expansion of long bones, with increased susceptibility to breakage due to applied physical stress [3,9,10].…”

Structural analysis of reactionary dentin formed in response to polymicrobial invasion

“…The intense Zn signal in Rd could also be explained by the occurrence of less soluble Zn phosphate providing the critical nuclei for subsequent precipitation of calcium phosphate. Zinc deficiencies result in abnormal cartilage development, irregular bone formation and increase in bone deformity (Bergman et al, 1970; Da Cunha Ferreira et al, 1991; Westmoreland and Hoekstra, 1969). The stronger signal for carbon detected in Rd could relate to the increase of representation of organic compounds during reactionary dentin formation (Charadram et al, 2012).…”

Regulatory Roles of Zinc in Matrix Vesicle-Mediated Mineralization of Growth Plate Cartilage

“…Moreover, Zn 2ϩ treatment of mouse calvaria organ cultures led to decreased mineralization, whereas extensive cartilage mineralization was observed in Zn 2ϩ -deficient rats. (20,45) All of these findings indicate that Zn 2ϩ plays a major role as an inhibitory factor in controlling mineralization of skeletal tissues.…”

“…(15)(16)(17) Experimental Zn 2ϩ deficiencies have been demonstrated to result in abnormal cartilage development, irregular and increased cartilage mineralization, and bone deformities. (18)(19)(20) On the other hand, increased levels of Zn 2ϩ are associated with decreased mineralization, which results in a disease known as osteochondrosis. (21) The effect of Zn 2ϩ on the function of MVs remains controversial.…”