Cadmium exposure during pregnancy and lactation: materno-fetal and newborn repercussions of Cd(II), and Cd–metallothionein complexes

Abstract

Cadmium (Cd) is a non-physiological heavy metal that can be harmful at low concentrations. Increasing anthropogenic activities are incrementing the risk of accumulation of this heavy metal in different organs and tissues of the body. In the case of pregnant women, the threat is more serious due to the implications affecting not only their own health but also fetal development as well. Metallothioneins (MTs), small cysteine-rich proteins, are involved in zinc (Zn) and copper homeostasis in mammals but can, however, also bind with Cd if present. The accumulation of Cd in maternal tissues (e.g. placenta, maternal blood, and mammary glands) induces the synthesis of MTs, preferably MT2, in an attempt to sequester the metal to avoid toxicity. The formed Cd–MT complexes will avoid the Cd transport from the placenta to the fetus and end up accumulating in the maternal kidneys. At the same time, high concentrations of MTs will increase the formation of Zn–MT complexes, therefore decreasing the amount of Zn ions available to be transported to the fetus by means of Zn transporters such as ZnT2, ZIP14 and DMT1. Although MTs cannot transport Cd from the mother to the fetus, the divalent DMT1 transporter is suggested to carry the metal to the fetus. As a consequence, the low levels of Zn(II) in the fetus, together with the presence of Cd(II) coming from the mother either via the placenta and cord blood or via breast milk induce changes in the fetal development including fetal growth retardation, and low weight or height of the newborn. Likewise, the concentrations of Cd(II) in the newborn can cause alterations such as cognitive disabilities. In summary, the presence of Cd(II) in the maternal tissues will induce MT synthesis in an attempt to detoxify these tissues and reduce the possible toxicity of Cd in fetal and newborn tissues