Combined ex vivo and in vivo evaluation of dolutegravir embryotoxicity: NTDs and yolk sac vascular abnormalities

• Dolutegravir (DTG) exposure induces neural tube defects (NTDs) and yolk sac vascular abnormalities in a dose-dependent manner in both ex vivo whole embryo culture and in vivo mouse models. • Mechanistically, DTG triggers oxidative stress, activating the Nrf2-SOD1/CAT antioxidant axis, but ultimately leads to increased apoptosis and suppressed proliferation, impairing yolk sac vasculogenesis and neural tube closure. • The study provides critical evidence for the potential embryotoxicity of DTG, emphasizing the need for careful risk assessment in pregnant women using this antiretroviral drug. • These findings highlight the importance of evaluating DTG's safety profile in clinical settings, especially for women of childbearing age, and may inform future guidelines for its use during pregnancy.