Abstract
BackgroundOxidative 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.MethodsThe 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 from d 85 of gestation to d 21 of lactation, respectively. Placenta, serum, and colostrum 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).ResultsCompared with the NBW placentae, the LBW placentae showed increased oxidative damage and were vulnerable to angiogenesis impairment. Particularly, H2O2-induced oxidative stress prompted intracellular reactive oxygen species generation and inhibited the tube formation and migration of PVECs as well as the expression of vascular endothelial growth factor-A (VEGF-A) in vitro. However, dietary CS supplementation can alleviate oxidative stress and improve the reproductive performance of sows. Specifically, compared with the control group, dietary 100 mg/kg CS could (1) decrease the stillbirth and invalid rates, and increase both the piglet birth weight in the low yield sows and the placental efficiency; (2) increase glutathione and reduce malondialdehyde in both the serum and the colostrum of sows; (3) increase the levels of total antioxidant capacity and glutathione in LBW placentae; (4) increase the vascular density, the mRNA level of VEGF-A, and the immune-staining intensity of platelet endothelial cell adhesion molecule-1 in the LBW placentae. 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. Meanwhile, inhibition of Stat3 significantly decreased the cell viability, tube formation and the VEGF-A protein level in CS pretreated with H2O2-cultured PVECs.ConclusionsThe results indicated that oxidative stress and impaired angiogenesis might contribute to the occurrence of LBW 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 increasing birth weight in low yield sows and reducing stillbirth rate. The in vitro data showed that the underlying mechanism for the positive effects of CS might be related to the activation of Stat3 in PVECs.
Highlights
Pregnancy is an oxidative stress challenge for the mother, especially during the late gestation period [1], when the rapid development of the fetus increases the metabolic burdens on pregnant sows or dams, leading to elevated systemic oxidative stress [2, 3]
Correlation between birth weight and placental characteristics of piglets When compared with the NBW placenta, the LBW placenta showed significantly lower (P < 0.05) blood vessel density (Fig. 1A, B) and immunostaining intensity of CD31 (Fig. 1C, D)
Previous studies have shown that increased oxidative stress in placenta is associated with the occurrence of adverse pregnancy outcomes, including intrauterine growth restriction and stillbirth [22, 23], suggesting that oxidative stress might contribute to the occurrence of low birth weight and stillbirth
Summary
Pregnancy is an oxidative stress challenge for the mother, especially during the late gestation period [1], when the rapid development of the fetus increases the metabolic burdens on pregnant sows or dams, leading to elevated systemic oxidative stress [2, 3]. Increasing evidence indicates that maternal oxidative stress is associated with several adverse outcomes, such as gestational diabetes mellitus, proteinuria preeclampsia, postpartum hemorrhage, fetal death, and low birth weight [4, 5]. Our previous studies have uncovered that increased oxidative stress induced by maternal obesity may decrease the development of placental vasculature essential for fetal growth during pregnancy [10], suggesting the involvement of placental oxidative stress in the development of adverse pregnancy outcomes. An increased amount of reactive oxygen species (ROS) could induce autophagy, dysfunction, and apoptotic death of vascular endothelial cells [9]. 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
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