Retinoic Acid–PPARα Mediates β‑Carotene Resistance to Placental Dysfunction Induced by Deoxynivalenol

Deoxynivalenol (DON), one of the most polluted mycotoxins in the environment and food, has been proven to have strong embryonic and reproductive toxicities. However, the effects of DON on placental impairment and effective interventions are still unclear. This study investigated the effect of β-carotene on placental functional impairment and its underlying molecular mechanism under DON exposure. Adverse pregnancy outcomes were caused by intraperitoneal injection of DON from 13.5 to 15.5 days of gestation in mice, resulting in higher enrichment of DON in placenta than in other tissue samples. Interestingly, 0.1% β-carotene dietary supplementation could significantly alleviate DON-induced pregnancy outcomes. Additionally, in vivo and in vitro placental barrier models demonstrated the association of DON-induced placental function impairment with placental permeability barrier disruption, angiogenesis impairment, and oxidative stress induction. Moreover, β-carotene regulated DON-induced placental toxicity by activating the expressions of claudin 1, zonula occludens-1, and vascular endothelial growth factor-A through retinoic acid–peroxisome proliferator-activated receptor α signaling.