Background: Pregnancy has been identified as a risk factor for severe COVID-19, leading to maternal and neonatal complications. The safety and effects of the SARS-CoV-2 vaccination during pregnancy, particularly on placental function and oxidative stress (OxS), remain underexplored. We investigated the impact of vaccination on third-trimester placental antioxidant defense markers. Methods: Ninety full-term pregnant women were divided into the following groups: vaccinated (n = 27) and unvaccinated (n = 25) COVID-19-positive pregnant women; control subgroups were composed of vaccinated (n = 19) or unvaccinated (n = 19) COVID-19-negative women with a healthy term singleton pregnancy with no signs of COVID-19. Placental samples were collected after delivery. Lipid peroxidation (TBARS), gene expression of HIF-1α, and catalase (CAT), superoxide dismutase-1 (SOD1) and CAT-SOD1 enzymatic activity were measured. Results: COVID-19-positive placentae exhibited significantly higher TBARS and HIF-1α levels compared to controls, regardless of vaccination status. Vaccination significantly increased placental CAT and SOD1 expression and activity in COVID-19-positive women, suggesting enhanced antioxidant defense. Unvaccinated women showed a higher incidence of COVID-19 symptoms and lower antioxidant enzyme activity. Conclusions: SARS-CoV-2 infection induced placental OxS, which is countered by a placental adaptive antioxidant response. Vaccination during pregnancy enhances placental defense, further supporting the safety and benefits of COVID-19 vaccination in preventing complications and protecting fetal development.
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