Maternal supply of cysteamine alleviates oxidative stress and enhances angiogenesis in porcine placenta.
Maternal supply of cysteamine alleviates oxidative stress and enhances angiogenesis in porcine placenta.
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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
DOI：
10.1186/s40104-021-00609-8
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发表时间：
2021-08-10
影响因子：
7
通讯作者：
Tan C
中科院分区：
文献类型：
--
作者：
Huang S;Wu Z;Huang Z;Hao X;Zhang L;Hu C;Wei J;Deng J;Tan C
背景：胎盘氧化应激与母猪不良妊娠结局的发生有关，但目前尚无令人满意的治疗策略。本研究探讨了半胱胺（CS）作为一种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。方法测定出生体重< 1.0 kg（低出生体重，LBW）和1.4 ~ 1.6 kg（正常出生体重，NBW）仔猪的胎盘氧化应激状态和血管密度，并将84头母猪分为4个处理（n= 21），分别在妊娠第85天至泌乳第21天在基础饲粮中添加0、100、300和500 mg/kg的CS。采集母猪或仔猪胎盘、血清和初乳样品，记录母猪和仔猪的特征。此外，用猪血管内皮细胞（pvec）验证了他们的体内结果。结果与NBW组相比，LBW组胎盘氧化损伤加重，血管生成功能受损。特别是h2o2诱导的氧化应激促进了细胞内活性氧的产生，抑制了pvec的管状形成和迁移以及血管内皮生长因子- a （VEGF-A）的体外表达。然而，饲粮中添加CS可减轻母猪氧化应激，提高母猪繁殖性能。具体而言，与对照组相比，饲粮添加100 mg/kg CS可(1)降低低产猪死产率和废产率，提高仔猪初生重和胎盘效率；(2)提高母猪血清和初乳中的谷胱甘肽水平，降低丙二醛水平；(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预处理可以显著逆转h2o2诱导的NADPH氧化酶2- ros介导的信号转导和转录激活因子3 （Stat3）信号通路失活，抑制pvec的增殖、成管和迁移。同时，抑制Stat3显著降低h2o2培养pvec预处理CS的细胞活力、成管及VEGF-A蛋白水平。结论妊娠期LBW仔猪的发生可能与氧化应激和血管生成障碍有关，但妊娠后期和哺乳期母猪添加100 mg/kg的CS可缓解氧化应激，促进胎盘血管生成，从而提高低产仔母猪的出生重，降低死胎率。他们的体外实验数据显示，CS积极作用的潜在机制可能与pvec中Stat3的激活有关。
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, thein vivoresults 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 ofVEGF-A, and the immune-staining intensity of platelet endothelial cell adhesion molecule-1 in the LBW placentae. Furthermore, thein vitroexperiment 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 H2O2inhibition 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. Thein vitrodata showed that the underlying mechanism for the positive effects of CS might be related to the activation of Stat3 in PVECs.
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