Maternal Supply of Cysteamine during Late Gestation Alleviates Oxidative Stress and Enhances Angiogenesis in Porcine Placenta

Abstract Background: Oxidative stress in placenta is associated with the occurrence of adverse pregnancy outcomes in sow, but there are few satisfactory treatment strategies for these conditions. This study investigated the potential of cysteamine (CS) as an antioxidant protectant for regulating the reproductive performance, redox status, and placental angiogenesis of sows.Methods: The placental oxidative stress status and vascular density of piglets with different birth weights: <1.0 kg (low birth weight, LBW) and 1.4-1.6 kg (normal birth weight, NBW) were evaluated, followed by allotting 84 sows to four treatments (n=21) and feeding them with a basal diet supplemented with 0, 100, 300, or 500 mg/kg of CS (CON, CS100, CS300, and CS500 diet) from day 85 of gestation to day 21 of lactation, respectively. Placentae, serum and colostrum, and blood samples of sows or piglets were collected, and the characteristics of sows and piglets were recorded. Furthermore, the in vivo results were validated using porcine vascular endothelial cells (PVECs).Results: The placentae for the LBW piglets had higher oxidative damage and lower vascular density than those for the NBW piglets (P < 0.05). Further experiments with sows showed that compared with the CON group, the CS100 group was lower in the stillbirth and invalid rates, and higher in the piglet birth weight and placental efficiency (P < 0.05). Meanwhile, the CS100 group also displayed higher glutathione and lower malondialdehyde in both the serum and colostrum of sows (P < 0.05). Interestingly, compared to the CON group, the LBW placentae of the CS100 group showed a decrease in oxidative damage, while an increase in vascular density (P < 0.05), as well as the mRNA level of vascular endothelial growth factor A and the immunostaining intensity of platelet endothelial cell adhesion molecule-1 (P < 0.05). Furthermore, the in vitro experiment indicated that CS pre-treatment could significantly reverse the NADPH oxidase 2-ROS-mediated inactivation of signal transducer and activator of transcription-3 (Stat3) signaling pathway induced by H2O2 inhibition of the proliferation, tube formation, and migration of PVECs (P < 0.05).Conclusions: The results indicated that oxidative stress and impaired angiogenesis might contribute to the occurrence of low-birth-weight piglets during pregnancy, but CS supplementation at 100 mg/kg during late gestation and lactation of sows could alleviate oxidative stress and enhance angiogenesis in placenta, thereby improving pregnancy outcome. The in vitro data showed that the underlying mechanism for the positive effects of CS may be related to the activation of Stat3.