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. 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 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). Compared 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. The 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.

中文翻译：

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母体供应半胱胺可减轻猪胎盘的氧化应激并增强血管生成

胎盘氧化应激与母猪不良妊娠结局的发生有关，但针对这些情况几乎没有令人满意的治疗策略。本研究调查了半胱胺 (CS) 作为抗氧化保护剂调节母猪繁殖性能、氧化还原状态和胎盘血管生成的潜力。评估不同出生体重的仔猪的胎盘氧化应激状态和血管密度：<1.0 kg（低出生体重，LBW）和1.4-1.6 kg（正常出生体重，NBW），然后将84头母猪分配到四个处理组（n = 21），并从妊娠第 85 天到哺乳第 21 天分别用补充有 0、100、300 或 500 mg/kg CS 的基础饮食喂养。采集母猪或仔猪的胎盘、血清和初乳样本，记录母猪和仔猪的特征。此外，使用猪血管内皮细胞（PVEC）验证了体内结果。与 NBW 胎盘相比，LBW 胎盘表现出更高的氧化损伤，并且容易受到血管生成障碍。特别是，H2O2诱导的氧化应激促进细胞内活性氧的产生，抑制PVEC的管形成和迁移以及体外血管内皮生长因子-A（VEGF-A）的表达。然而，日粮中补充CS可以缓解氧化应激并提高母猪的繁殖性能。具体而言，与对照组相比，日粮中添加100 mg/kg CS可以：（1）降低死胎率和病死率，提高低产母猪的仔猪初生重和胎盘效率；(2)增加母猪血清和初乳中的谷胱甘肽，减少丙二醛；(3)提高LBW胎盘总抗氧化能力和谷胱甘肽水平；(4)增加LBW胎盘血管密度、VEGF-A mRNA水平和血小板内皮细胞粘附分子-1免疫染色强度。此外，体外实验表明，CS预处理可以显着逆转NADPH氧化酶2-ROS介导的信号转导子和转录激活子3（Stat3）信号通路的失活，该信号通路由H2O2抑制增殖、管形成和细胞增殖诱导。 PVEC 的迁移。同时，抑制 Stat3 显着降低用 H2O2 培养的 PVEC 预处理的 CS 中的细胞活力、管形成和 VEGF-A 蛋白水平。结果表明，氧化应激和血管生成受损可能导致妊娠期仔猪低体重的发生，但母猪妊娠后期和哺乳期补充100 mg/kg CS可减轻氧化应激并增强胎盘血管生成，从而增加仔猪初生重。母猪产量低，降低死产率。