School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS, UK.
School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS, UK; School of Human Sciences, University of Derby, Kidleston Road, Derby DE22, 1GB, UK.
Biochem Pharmacol. 2019 Jun;164:289-298. doi: 10.1016/j.bcp.2019.04.023. Epub 2019 Apr 22.
Adequate invasion and complete remodelling of the maternal spiral arteries by the invading extravillous trophoblasts are the major determinants of a successful pregnancy. Increase in oxidative stress during pregnancy has been linked to the reduction in trophoblast invasion and incomplete conversion of the maternal spiral arteries, resulting in pregnancy complications such as pre-eclampsia, intrauterine growth restriction, and spontaneous miscarriages resulting in foetal/maternal mortality. The use of antioxidant therapy (vitamin C and E) and other preventative treatments (such as low dose aspirin) have been ineffective in preventing pre-eclampsia. Also, as the majority of antihypertensive drugs pose side effects, choosing an appropriate treatment would depend upon the efficacy and safety of mother/foetus. Since pre-eclampsia is mainly linked to placental oxidative stress, new diet-based antioxidants can be of use to prevent this condition. The antioxidant properties of flavonoids (naturally occurring phenolic compounds which are ubiquitously distributed in fruits and vegetables) have been well documented in non-trophoblast cells. Therefore, this study aimed to investigate the effects of flavonoids (quercetin, hesperidin) and their metabolites (Quercetin 3-O-β-glucuronide and hesperetin), either alone or in combination, on first trimester trophoblast cell line HTR-8/SVneo during oxidative stress. The data obtained from this study indicate that selected flavonoids, their respective metabolites significantly reduced the levels of reduced glutathione (p < 0.0001) during HR-induced oxidative stress. These flavonoids also inhibited the activation of pro-apoptotic kinases (p38 MAPK and c-Jun N-terminal kinase) during HR-induced phosphorylation. In addition, they enhanced spheroid stem-like cell generation from HTR8/SVneo cells, aiding their invasion. Our data suggest that dietary intake of food rich in quercetin or hesperidin during early pregnancy can significantly improve trophoblast (placenta) health and function against oxidative stress.
充足的滋养细胞浸润和螺旋动脉的完全重塑是成功妊娠的主要决定因素。妊娠期间氧化应激的增加与滋养细胞浸润减少和螺旋动脉不完全转化有关，导致妊娠并发症，如子痫前期、宫内生长受限和自发流产导致胎儿/母亲死亡。抗氧化治疗（维生素 C 和 E）和其他预防治疗（如低剂量阿司匹林）的使用并未有效预防子痫前期。此外，由于大多数降压药都有副作用，选择合适的治疗方法取决于母亲/胎儿的疗效和安全性。由于子痫前期主要与胎盘氧化应激有关，新的基于饮食的抗氧化剂可以用于预防这种情况。类黄酮（广泛存在于水果和蔬菜中的天然酚类化合物）的抗氧化特性在非滋养细胞中已有很好的记载。因此，本研究旨在研究类黄酮（槲皮素、橙皮苷）及其代谢物（槲皮素 3-O-β-葡萄糖醛酸和橙皮苷）单独或联合使用对氧化应激下第一孕期滋养细胞系 HTR-8/SVneo 的影响。本研究获得的数据表明，选定的类黄酮及其各自的代谢物在 HR 诱导的氧化应激期间显著降低了还原型谷胱甘肽的水平（p<0.0001）。这些类黄酮还抑制了 HR 诱导的磷酸化过程中促凋亡激酶（p38 MAPK 和 c-Jun N-末端激酶）的激活。此外，它们还增强了 HTR8/SVneo 细胞中球体样干细胞的生成，促进了它们的侵袭。我们的数据表明，妊娠早期摄入富含槲皮素或橙皮苷的食物可以显著改善滋养细胞（胎盘）的健康和功能，抵御氧化应激。
