Copper homeostasis and pregnancy complications: a comprehensive review

Pregnancy complications pose challenges for both pregnant women and obstetricians globally, with the pathogenesis of many remaining poorly understood. Recently coined as a mode of cell death, cuproptosis has been proposed but remains largely unexplored. This process involves copper overload, resulting in the accumulation of fatty acylated proteins and subsequent loss of iron-sulfur cluster proteins. This cascade induces proteotoxic stress, leading to cell death. In recent years, studies have indicated a connection between abnormal copper metabolism and several pregnancy-related diseases, including maternal placental dysplasia, gestational diabetes mellitus (GDM), gestational hypertension (PIH), preterm birth or abortion, as well as conditions in offspring such as intrauterine growth restriction (IUGR), allergic disease, Menkes disease, and Wilson's disease. Investigating the mechanism of cuproptosis and abnormal copper metabolism in these pregnancy-related diseases emerges as a critical research area. This article provides a concise review of cuproptosis mechanisms and emphasizes the association between abnormal copper metabolism and pregnancy-related diseases. Nevertheless, the doubtful viewpoints were also discussed.