**7. Consequences of Redox Deregulation**

In accordance with the current biochemical literature, redox regulation is tightly regulated in the spermatozoa, with interactions between spermatic metabolism, mitochondrial production and scavenging of ROS. A summary of current knowledge on redox regulation in stallion spermatozoa is presented in Figure 1. Many factors can deregulate this complex network in humans and other animals, including aging, exposure to toxins, particularly alcohol and tobacco in humans, poor diet, lack of physical activity and systemic diseases including obesity and diabetes [30,155–158]. Also, current sperm biotechnologies such as cryopreservation cause redox deregulation of spermatozoa, mainly through a severe mitochondrial osmotic stress [110,118,128,159,160]. Deregulation of redox homeostasis has a profound impact on sperm physiology and fertility, all spermatic compartments and functions may be a ffected. Moreover, impacts on the embryo and the o ffspring may also occur.

**Figure 1.** Overview of redox regulation in stallion spermatozoa. Electron (e−) leakage at the mitochondria is one of the main sources of ROS. Mechanisms to maintain redox homeostasis include thioredoxin (TRX) and peroxiredoxin (PRDX) systems and gluthatione (GSH) (green boxes). The stallion spermatozoa can incorporate cystine (cyss) (blue boxes), through the SlC7A11 x-CT antiporter by exchange for intracellular glutamate (Glut). Cystine is reduced in the cytoplasm to Cysteine and contribute to the intracellular GSH pool by the action of the enzymes involved in the synthesis of GHS, Glutathion syntethase (GSS) and glutamate cysteine ligase (GCLC); this mechanism has been described only in horses. Controlled levels of ROS regulate sperm functionality through reversible oxidation of thiols in cysteine containing proteins (blank boxes). If redox regulation is lost, irreversible oxidation of thiols and oxidative attack to lipids DNA and proteins occurs leading to sperm malfunction and finally death (red boxes). The hydroxyl radical (OH•) is the most damaging ROS, produced by the Habor–Weiss/Fenton reaction.
