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Abstract

Despite a significant number of anatomical, genetic and chromosomal studies, the problem of recurrent miscarriage (RM) is still one of the challenges in reproductive medicine, as in almost 50% of the cases no clear cause is found. These are unexplained cases that are frequently called idiopathic RM and indicate that there might be an underlying molecular and biochemical mechanism that is not routinely checked during clinical practice. This review focuses on the key role of oxidative stress and redox imbalance in the pathogenesis of idiopathic RM. A special focus is placed on mitochondrial dysfunction, which results in increased electron leakage from the mitochondrial respiratory chain and thus increased production of reactive oxygen species (ROS), that leads to lipid peroxidation and the formation of toxic byproducts like malondialdehyde (MDA). Additionally, the role of the environmental conditions in the Middle East, such as exposure to heavy metals such as depleted uranium or zinc and selenium deficiencies/imbalances, are explored. These may compromise antioxidant mechanisms, such as superoxide dismutase (SOD) and glutathione peroxidase (GPx), and further increase oxidative damage. Additionally, oxidative stress can affect immune regulation by inducing pro-inflammatory responses, NETosis and ferroptosis, which is a regulated cell death dependent on iron, linked with placental dysfunction and premature placental aging. The overall findings suggest that idiopathic RM is a disorder of oxidative and metabolic regulation. A personalized redox medicine strategy that targets the restoration of mitochondrial function and cellular homeostasis could be useful in future therapeutic strategies.

First Page

197

Last Page

210

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