Molecular Regulation of Copper Homeostasis in the Male Gonad during the Process of Spermatogenesis

Abstract

Owing to its redox properties, copper is a cofactor of enzymes that catalyze reactions in fundamental metabolic processes. However, copper–oxygen interaction, which is a source of toxic oxygen radicals generated by the Fenton reaction, makes copper a doubled-edged-sword in an oxygen environment. Among the microelements influencing male fertility, copper plays a special role because both copper deficiency and overload in the gonads worsen spermatozoa quality and disturb reproductive function in mammals. Male gametes are produced during spermatogenesis, a multi-step process that consumes large amounts of oxygen. Germ cells containing a high amount of unsaturated fatty acids in their membranes are particularly vulnerable to excess copper-mediated oxidative stress. In addition, an appropriate copper level is necessary to initiate meiosis in premeiotic germ cells. The balance between essential and toxic copper concentrations in germ cells at different stages of spermatogenesis and in Sertoli cells that support their development is handled by a network of copper importers, chaperones, recipient proteins, and exporters. Here, we describe coordinated regulation/functioning of copper-binding proteins expressed in germ and Sertoli cells with special emphasis on copper transporters, copper transporting ATPases, and SOD1, a copper-dependent antioxidant enzyme. These and other proteins assure copper bioavailability in germ cells and protection against copper toxicity.

Long-term copper exposure promotes apoptosis and autophagy by inducing oxidative stress in pig testis

“…The Cu ion entry into cells is mediated by Cu transporters (CTR), and 80% of Cu ion is transported into the cell by CTR1, which is encoded by Slc31a1 gene (Ogórek et al 2017 ). The intracellular Cu ions are supplied to SOD1 and metallothionein (MT), and excessive Cu ions will bind to the ATOX1 protein and then be transported to ATP7A and ATP7B, which can transport Cu ions to outside the cell or into the blood, respectively (Herman et al 2020 ). The upregulated expression of the testicular copper transporter gene indicated that the concentrations of Cu in the testicular cells was beyond the range of tolerance in testicular cells; for that, Cu transporter gene expression was elevated in order to maintain testicular cell homeostasis.…”

Histopathological and Biochemical Comparative Study of Copper Oxide Nanoparticles and Copper Sulphate Toxicity in Male Albino Mice Reproductive System

“…A previous study [ 33 ] reported the presence of small amounts of these substances in the interstitial tissue of the testes and the adverse effects in the germ. Moreover, the high quantity of unsaturated fatty acids in the germ cell membranes made the germ cell more vulnerable to oxidative stress caused by the presence of an excessive amount of copper [ 34 ].…”

Targeting the Copper Transport System to Improve Treatment Efficacies of Platinum-Containing Drugs in Cancer Chemotherapy

“…It is important to note that the majority of cellular Cu is bound by cellular constituents and only a small fraction is free Cu for exchange. For example, about 90% of Cu in the circulation is bound by ceruloplasmin and the other 10% is bound by albumin, histidine, GSH, and transferrin [81,82]. At the intracellular level, in the entire process of Cu(I) transport system, from hCtr1 to the ATPases, Cu(I) movements involve directly coordinate transfers between donor and recipient molecules without metal dissociation.…”