Punicalagin improves chorioallantoic and yolk sac vasculogenesis and teratogenesis of embryos induced by nicotine exposure

Punicalagin is a functional ingredient in pomegranate juice, which has various beneficial effects for health and prevention of disease. In this study, the anti-teratogenic effect of punicalagin (1 × 10−5 or 1 × 10−4  µM) was investigated in cultured mouse embryos and yolk sac-placentas exposed to nicotine (1 mM), one of the main toxins in cigarette smoke. Nicotine-treated embryos revealed severe anomalies as well as impaired yolk sac vascularization, reduced labyrinth formation, and developmental arrest of blood islands in the chorioallantoic border. Furthermore, nicotine significantly altered the regulations of hypoxia- and vascularization-related genes in yolk sac-placenta and the levels of oxidative stress, apoptosis, and inflammation in both embryos and yolk sac-placentas. However, these detrimental changes were remarkably improved in response to co-treatment with punicalagins. These findings indicate that punicalagin could be crucial to the development of clinical strategies to attenuate nicotine-induced teratogenesis in embryos.