Review of the Role of Ferroptosis in Testicular Function

Abstract

Iron is an important metal element involved in the regulation of male reproductive functions and has dual effects on testicular tissue. A moderate iron content is necessary to maintain testosterone synthesis and spermatogenesis. Iron overload can lead to male reproductive dysfunction by triggering testicular oxidative stress, lipid peroxidation, and even testicular ferroptosis. Ferroptosis is an iron-dependent form of cell death that is characterized by iron overload, lipid peroxidation, mitochondrial damage, and glutathione peroxidase depletion. This review summarizes the regulatory mechanism of ferroptosis and the research progress on testicular ferroptosis caused by endogenous and exogenous toxicants. The purpose of the present review is to provide a theoretical basis for the relationship between ferroptosis and male reproductive function. Some toxic substances or danger signals can cause male reproductive dysfunction by inducing testicular ferroptosis. It is crucial to deeply explore the testicular ferroptosis mechanism, which will help further elucidate the molecular mechanism of male reproductive dysfunction. It is worth noting that ferroptosis does not exist alone but rather coexists with other forms of cell death (such as apoptosis, necrosis, and autophagic death). Alleviating ferroptosis alone may not completely reverse male reproductive dysfunction caused by various risk factors.

NAD+ precursors promote the restoration of spermatogenesis in busulfan-treated mice through inhibiting Sirt2-regulated ferroptosis

“…Moreover, abnormal protein levels of GPX4, COX2, ACSL4, NCOA4, FTH1, as well as alterations in the content of GSH and NADPH, serve as biomarkers of ferroptosis. Presently, a connection between ferroptosis and male reproduction disorder has been established 39 . In fact, some studies have reported that the induction of testicular oxidative stress leading to ferroptosis by substances such as arsenite, copper, and PM2.5 particles 33 , 40 , 41 , while Di (2-ethylhexyl) phthalate has been shown to induce ferroptosis via HIF-1α/HO-1 signaling pathway and transferrin receptor 1 , 42 .…”

Ferroptosis: Emerging mechanisms, biological function, and therapeutic potential in cancer and inflammation

“…Glutathione (GSH) is a tripeptide consisting of glycine, cysteine, and glutamic acid-containing Y-amido-hexapeptide and sulfhydryl groups, which is an important antioxidant [ 40 , 41 ]. GSH functions intracellularly as a vital substrate for GPX4 [ 42 ].…”

Overview of T-2 Toxin Enterotoxicity: From Toxic Mechanisms and Detoxification to Future Perspectives

“…Including 0.2 mg/kg SeMet in feed has been shown to effectively reduce ROS and MDA levels and enhance SOD and GSH-Px activity. 65,66 Se can also alleviate the inflammatory response of the jejunum and enhance ZO-1 and occludin expression to preserve the integrity of the intestinal barrier. Se has demonstrated strong antioxidant properties to protect against mycotoxins.…”

“…The results showed that the ROS level in the small intestine was markedly elevated and that antioxidant activity and the expression of occludin and ZO-1 were considerably decreased. Including 0.2 mg/kg SeMet in feed has been shown to effectively reduce ROS and MDA levels and enhance SOD and GSH-Px activity. , Se can also alleviate the inflammatory response of the jejunum and enhance ZO-1 and occludin expression to preserve the integrity of the intestinal barrier. Se has demonstrated strong antioxidant properties to protect against mycotoxins.…”