Environmental cadmium exposure during pregnancy causes diabetes-like phenotypes in mouse offspring: Association with oxidative stress in the fetal liver.

Song-Jia Yi, Yong-Wei Xiong, Hua-Long Zhu, Li-Min Dai, Xue-Lin Cao, Wei-Bo Liu, Xue-Ting Shi, Guo-Xiang Zhou, A-Ying Liu, Ling-Li Zhao, Cheng Zhang, Lan Gao, De-Xiang Xu, Hua Wang

The Science of the total environment 2021 Jul 10

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Cadmium (Cd), a noxious heavy metal, is widespread in the living environment. Gestational exposure to Cd at environmental dose has been shown to cause fetal growth restriction (FGR). However, the long-term effects and the mechanisms underlying environmental Cd exposure on glucose metabolism in offspring remain unclear. Here, we established a murine model to study the impacts of gestational exposure to environmental Cd on glucose metabolism at different life stages of offspring. Results demonstrated that the offspring mice developed hyperglycemia in puberty and impaired glucose tolerance in adulthood following maternal Cd exposure during gestation. Further mechanistic investigation showed that Cd exposure upregulated the expression of key proteins in hepatic gluconeogenesis, including p-CREB, PGC-1α and G6PC, in pubertal and adult offspring. In addition, we demonstrated that Cd exposure during pregnancy markedly elevated the level of oxidative stress-related proteins, including NOX2, NOX4 and HO-1, in the fetal liver. The effects of gestational exposure to N-acetylcysteine (NAC), a free-radical scavenging antioxidant, presented that NAC supplementation alleviated hepatic oxidative stress in fetuses, and thereby reversed hyperglycemia and glucose intolerance in mouse offspring. Collectively, our data suggested that gestational exposure to environmental Cd caused diabetes-like phenotypes via enhancing hepatic gluconeogenesis, which is associated with oxidative stress in fetal livers. This work provides new insights into the protective effects of antioxidants on fetal-originated diabetes triggered by environmental toxicants. Copyright © 2021 Elsevier B.V. All rights reserved.

Citation

Song-Jia Yi, Yong-Wei Xiong, Hua-Long Zhu, Li-Min Dai, Xue-Lin Cao, Wei-Bo Liu, Xue-Ting Shi, Guo-Xiang Zhou, A-Ying Liu, Ling-Li Zhao, Cheng Zhang, Lan Gao, De-Xiang Xu, Hua Wang. Environmental cadmium exposure during pregnancy causes diabetes-like phenotypes in mouse offspring: Association with oxidative stress in the fetal liver. The Science of the total environment. 2021 Jul 10;777:146006