The Role of ROS as a Double-Edged Sword in (In)Fertility: The Impact of Cancer Treatment.

Abstract

Simple SummaryTumor cells are highly resistant to oxidative stress, but beyond a certain threshold, it may lead to apoptosis/necrosis. Thus, induced loss of redox balance can be a strategy used in anticancer therapies. However, the effectiveness of drugs contrasts with unknown mechanisms involved in the loss of fertility. Considering that cancer patients’ life expectancy is increasing, it raises concerns about the unknown adverse effects. Therefore, new strategies should be pursued alongside explaining to the patients their options regarding the reproduction side effects.Tumor cells are highly resistant to oxidative stress resulting from the imbalance between high reactive oxygen species (ROS) production and insufficient antioxidant defenses. However, when intracellular levels of ROS rise beyond a certain threshold, largely above cancer cells’ capacity to reduce it, they may ultimately lead to apoptosis or necrosis. This is, in fact, one of the molecular mechanisms of anticancer drugs, as most chemotherapeutic treatments alter redox homeostasis by further elevation of intracellular ROS levels or inhibition of antioxidant pathways. In traditional chemotherapy, it is widely accepted that most therapeutic effects are due to ROS-mediated cell damage, but in targeted therapies, ROS-mediated effects are mostly unknown and data are still emerging. The increasing effectiveness of anticancer treatments has raised new challenges, especially in the field of reproduction. With cancer patients’ life expectancy increasing, many aiming to become parents will be confronted with the adverse effects of treatments. Consequently, concerns about the impact of anticancer therapies on reproductive capacity are of particular interest. In this review, we begin with a short introduction on anticancer therapies, then address ROS physiological/pathophysiological roles in both male and female reproductive systems, and finish with ROS-mediated adverse effects of anticancer treatments in reproduction.