Lithium Exposure Causes Trophoblast Cuproptosis by Upregulating FOXO1/STEAP4 Axis in Unexplained Miscarriage.

ABSTRACT: Lithium (Li) batteries have been used worldwide, but few are recycled, thus, the waste Li has been widely spread into the environment and finally accumulated in human body. Cuproptosis is a newly reported Cu-dependent and programmed cell death form. The unclear pathogenesis of unexplained miscarriage (UM) largely restricts its clinical treatment and global human reproduction. In this study, a UM case-control study shows that Li levels in serum or villous tissues, the levels of cuproptosis in villous tissue, and UM are positively associated. Li-exposed mouse models further confirm that Li exposure causes placental cuproptosis to induce miscarriage. Mechanistically, Li exposure up-regulates FOXO1 expression levels and thus promotes FOXO1-mediated STEAP4 transcription, up-regulating STEAP4 le

SUBMITTER: Xing S 

PROVIDER: S-EPMC12520556 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature