Oxidative stress, placental ageing‐related pathologies and adverse pregnancy outcomes

Abstract

Oxidative stress (OS), an imbalance between free radical generation and antioxidant defence, is recognized as a key factor in the pathogenesis of adverse pregnancy outcomes. Although OS is a common future of normal pregnancy, persistent, overwhelming OS leads to consumption and decline of antioxidants, affecting placental antioxidant capacity and reducing systems. The accumulation of OS causes damage to lipids, proteins and DNA in the placental tissue that induces a form of accelerated ageing.Premature ageing of the placenta is associated with placental insufficiency that prevents the organ meeting the needs of the foetus, and as a consequence, the viability of the foetus is compromised. This review summarizes the literature regarding the role of OS and premature placental ageing in the pathophysiology of pregnancy complications. K E Y W O R D Sintrauterine growth restriction, oxidative stress, placental ageing, pre-eclampsia, preterm birth, senescence, stillbirth | INTRODUCTIONAll living organisms have limited life cycles, and ageing is part of that life cycle. Each organ within an organism also exhibits ageing-related changes; the placenta is no exception. The placenta, a specialized organ formed during pregnancy, grows throughout gestation, performs multiple functions, including endocrine regulation and nourishment of the foetus, 1 but also ages and is discarded at the end of pregnancy, while the foetus may live for another hundred years. So placental ageing is a normal physiologic phenomenon. 2 However, there are likely to be some placentas which show signs of ageing earlier than others, in the same way as some individuals age more quickly than others. Premature ageing and degenerative changes in the placenta may reduce the functional capacity of the placenta and lead to abnormal pregnancy outcomes. The placenta is the primary organ for transferring nutrients from the mother to the foetus, so growth and function of the placenta are precisely regulated and coordinated to ensure the optimal growth and development of the foetus. The placenta exchanges nutrients, for example oxygen, amino acids, carbohydrates, minerals and waste products, for example carbon dioxide between the maternal and foetal circulatory systems. 3 It releases hormones into both the maternal and foetal circulations to affect uterine function, maternal metabolism, foetal growth and development. Moreover, it metabolizes some substances and can release metabolic products into both foetal and maternal circulations. The placenta can help to protect the foetus against certain xenobiotic molecules, infections and maternal diseases. Therefore, the adequate function of this organ is crucial for a normal physiologic gestational process and a healthy baby as a final outcome.In this review, we focus on the role of OS in the pathophysiology of pregnancy complications, beginning with a brief overview of placental development at different stages of gestation. We then discuss the biochemical markers of ageing and OS-induced placental ageing.Finally, we disc...

Nitric oxide synthase and oxidative‐nitrosative stress play a key role in placental infection by Trypanosoma cruzi

“…The increase in RNA and this enzyme implies the possibility of a significant rise in its product, NO. 53,54 Our findings indicate that T. cruzi Oxidative stress is associated with placental hypoxia, the imbalance of cytokines, impairment of trophoblast invasion and implantation, which result in poor fetal development but with pathologies different to Chagas. 13,37 This phenomenon led us to postulate that NO may have been reacting with ROS and forming peroxynitrites.…”

Saturated and unsaturated fatty acids differentially regulate in vitro and ex vivo placental antioxidant capacity

“…Furthermore, it is well established that saturated fats such as PA are associated with the adverse effects of HFD consumption and obesity. 25 Although OS is a common feature of normal pregnancy, persistent, overwhelming OS leads to the consumption and decline of antioxidants, affecting placental antioxidant capacity and reducing systems. [20][21][22] However, to our knowledge, our study is the first to in- Oxidative stress can be defined as an imbalance between free radical generation and antioxidant defense and is recognized as a key factor in the pathogenesis of adverse pregnancy outcomes.…”

“…19. Previous studies have shown that PA induces cytotoxicity in a diverse set of cells including trophoblasts, skeletal muscle, and liver cells. 25 Indeed, the accumulation of OS causes damage to lipids, 25 Although OS is a common feature of normal pregnancy, persistent, overwhelming OS leads to the consumption and decline of antioxidants, affecting placental antioxidant capacity and reducing systems.…”

“…11,25 First trimester syncytiotrophoblasts, such as HTR-8 cells, serve as a good in vitro model for our studies, because they are more sensitive to oxygen-mediated damage than late-term trophoblasts, because as normal pregnancies progress, placental antioxidant protective mechanisms increase and lipid peroxidation decreases. 11,25 First trimester syncytiotrophoblasts, such as HTR-8 cells, serve as a good in vitro model for our studies, because they are more sensitive to oxygen-mediated damage than late-term trophoblasts, because as normal pregnancies progress, placental antioxidant protective mechanisms increase and lipid peroxidation decreases.…”

Maternal Oxidant-Antioxidant Homeostasis During Normotensive and Preeclamptic Pregnancy.

“…Oxidative stress is a common feature of normal pregnancy, but persistent, overwhelming OS leads to consumption and decline of antioxidants, affecting placental antioxidant capacity with subsequent damage of placental tissue components (9) ; thus inducing a form of accelerated placental ageing (10) . In addition, ROS could stimulate platelet adhesion and aggregation leading to intravascular coagulopathy with subsequent placental infarction and impairment of the uteroplacental blood flow (11) .…”