Toxic effects of maternal cadmium exposure on the metabolism and transport system of amino acids in the maternal livers

Fetal growth restriction (FGR) is one of the most common obstetric diseases, and affects approximately 10 % of all pregnancies worldwide. Maternal cadmium (Cd) exposure is one of the factors that may increase the risk of the development of FGR. However, its underlying mechanisms remain largely unknown. In this study, using Cd-treated mice as an experimental model, we analyzed the levels of some nutrients in the circulation and the fetal livers by biochemical assays; the expression patterns of several key genes involved in the nutrient uptake and transport, and the metabolic changes in the maternal livers were also examined by quantitative real-time PCR and gas chromatography-time of flight-mass spectrometry method. Our results showed that, the Cd treatment specifically reduced the levels of total amino acids in the peripheral circulation and the fetal livers. Concomi-tantly, Cd upregulated the expressions of three amino acid transport genes (SNAT4, SNAT7 and ASCT1) in the maternal livers. The metabolic profiling of maternal livers also revealed that, several amino acids and their derivatives were also increased in response to the Cd treatment. Further bioinformatics analysis indicated that the experimental treatment activated the metabolic pathways, including the alanine, aspartate and glutamate metabolism, valine, leucine and isoleucine biosynthesis, arginine and proline metabolism. These findings suggest that maternal Cd exposure activate the amino acid metabolism and increase the amino acid uptake in the maternal liver, which reduces the supply of amino acids to the fetus via the circulation. We suspect that this underlies the Cd-evoked FGR.

Automated summary

Fetal growth restriction (FGR) affects 10% of all pregnancies worldwide and maternal cadmium (Cd) exposure is a risk factor for FGR. This study used Cd-treated mice to investigate the mechanisms involved. Results showed that Cd treatment led to reduced levels of total amino acids in the circulation and fetal livers, and increased expression of amino acid transport genes in maternal livers. Metabolic profiling revealed an activation of various metabolic pathways. These findings suggest that Cd exposure activates amino acid metabolism and reduces the supply of amino acids to the fetus, potentially leading to FGR.