Trophoblast ferroptosis restricts SARS-CoV-2 spread in the placenta.

ABSTRACT: Prenatal SARS-CoV-2 infection is associated with adverse pregnancy outcomes, but placental mechanisms that restrict viral spread remain unclear. Here we show that SARS-CoV-2 exposure induces ferroptosis-linked iron dysregulation in the placenta as a host defense. Human placentas from early gestation SARS-CoV-2-exposed pregnancies exhibited persistent viral protein expression at term, iron accumulation, disrupted localization of iron transport proteins, and reduced expression of the ferroptosis inhibitor, GPX4. In trophoblast cells and newly generated stem cell-derived trophoblast organoids (SC-TOs) with physiological apical-out polarity, infection with live SARS-CoV-2 Delta variant suppressed expression of iron efflux transporter, ferroportin and ferroptosis inhibitors, GPX4 and PLA2G6, pr

SUBMITTER: McColl ER 

PROVIDER: S-EPMC12873918 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature