Disruption of Bone Zinc Metabolism during Postnatal Development of Rats after Early Life Exposure to Cadmium.

Sana Boughammoura,Safa Ben Mimouna,Marouen Chemek,Imed Messaoudi,Martine Cohen-Solal,Agnes Ostertag

doi:10.3390/ijms21041218

Abstract

This current study was conducted to investigate whether bone tissue impairment induced by early life exposure to cadmium (Cd) during postnatal development could result from disruption to zinc (Zn) metabolism. For this reason, the offspring from mothers receiving either tap water, Cd, Zn or Cd + Zn during gestation and lactation periods were euthanized at PND21 and PND70. At the end of the lactation period (PND21), our results showed that exposure to Cd increased Cd accumulation and Zn depletion in the femur. Furthermore, calcium (Ca) level was reduced. At the molecular level, Cd induced an increase of MT-1 expression and caused an upregulation of ZIP2 accompanied with a down-regulation of ZnT5. Runx2, ALP, colα-1 and Oc mRNA levels were also decreased. In plasma, IGF-1 and osteocalcin concentrations were decreased. Further, Cd altered femoral growth by generating changes in the growth plate. Consequently, the toxic effect of Cd persisted at adult age (PND70) by decreasing bone volume (%BV/TV), bone mineral density (BMD) and Ca content and by increasing trabecular separation (Tb.Sp) in the distal femur. Interestingly, Zn supply provided total or partial corrections of several toxic effects of Cd. These data suggest that the increases of Zn bioavailability as well as the reduction of Cd accumulation in the femur following the changes in ZIP2 and ZnT5 expression are part of the mechanism involved in Zn protection against Cd toxicity on bone tissue.

Highlights

Cadmium (Cd) is a toxic substance that is widely distributed in the environment and has a long biological half-life in organs
The current study is a continuous report in which we studied the effects on bone development in pups of rats from mothers treated by Cd and/or Zn during gestation and lactation and its consequences at adult age (PND70) in order to elucidate the mechanism likely to be involved in these effects
The same results have been reported by Chemek et al [26] which show that Cd accumulation affects Zn content in the testes of offspring from mothers treated with Cd during pregnancy and lactation

Summary

Introduction

Cadmium (Cd) is a toxic substance that is widely distributed in the environment and has a long biological half-life in organs. Liver, respiratory, cardiovascular systems, and bone are the most important target organs for Cd toxicity [1]. Several epidemiological studies have shown that relatively low exposure to this metal can lead to severe skeletal damage [2,3,4]. It has been reported that prolonged exposure to Cd may cause disruption in bone markers regulation [5] and in calcium metabolism [6], inducing osteomalacia [7] and a high risk of osteoporosis [8]. Studies have shown that Cd administration during gestation and lactation periods [9] leads to its accumulation in the mammary glands of female rodents. A number of neuro-toxicological and behavioral effects were observed during postnatal development [10]

Methods

Results

Conclusion