The Mammalian Testis-Specific Thioredoxin System

Abstract

Redox control of cell physiology is one of the most important regulatory mechanisms in all living organisms. The thioredoxin system, composed of thioredoxin and thioredoxin reductase, has emerged as a key player in cellular redox-mediated reactions. For many years, only one thioredoxin system had been described in higher organisms, ubiquitously expressed in the cytoplasm of eukaryotic cells. However, during the last decade, we and others have identified and characterized novel thioredoxin systems with unique properties, such as organelle-specific localization in mitochondria or endoplasmic reticulum, tissue-specific distribution mostly in the testis, and features novel for thioredoxins, such as microtubule-binding properties. In this review, we will focus on the mammalian testis-specific thioredoxin system that comprises three thioredoxins exclusively expressed in spermatids (named Sptrx-1, Sptrx-2, and Sptrx-3) and an additional thioredoxin highly expressed in testis, but also present in lung and other ciliated tissues (Txl-2). The implications of these findings in the context of male fertility and testicular cancer, as well as evolutionary aspects, will be discussed.

Spermatocyte/Spermatid-specific Thioredoxin-3, a Novel Golgi Apparatus-associated Thioredoxin, Is a Specific Marker of Aberrant Spermatogenesis

“…Processing of Bouin's fixed and paraffin-embedded testes and subsequent immunoperoxidase staining were described previously (8,32), with some modifications. After deparaffinization and hydration, testicular sections were either subjected or not to an antigen retrieval microwave technique (33); the antigen retrieval was found to have no advantage.…”

“…Procedures for electron microscopy immunocytochemistry were de-scribed previously (8). Affinity-purified anti-SPTRX-3 antibodies were used at a 1:20 dilution, and colloidal gold-conjugated goat anti-rabbit IgG at a 1:20 dilution was the secondary antibody.…”

“…DISCUSSION Redox regulation has been shown to be important in both the physiology of normal spermatogenesis and the cause of some spermatogenic abnormalities (47). We and others have recently identified several novel thioredoxins and thioredoxin reductases, most of them expressed in the male germ cell line (8,10,23). Our discovery of SPTRX-3 brings further complexity to this field and particularly to the testis-specific thioredoxin system, because at least five different SPTRX-3 alternative splicing variants exist.…”

“…Eukaryotic organisms have two ubiquitously expressed thioredoxin systems, one in cytoplasm composed of the Trx-1 and TrxR-1, and the other in mitochondria formed by Trx-2 and TrxR-2 (3). Furthermore, a large number of different thioredoxins with novel properties, such as organelle-specific localization in endoplasmic reticulum (6,7), tissue-specific distribution (8), and microtubule-binding properties (9), have recently been reported in mammals. This complexity is paralleled by the increasing number of splicing variants of both thioredoxin reductase genes.…”

PDILT, a Divergent Testis-specific Protein Disulfide Isomerase with a Non-classical SXXC Motif That Engages in Disulfide-dependent Interactions in the Endoplasmic Reticulum

“…A testis-specific homologue of calnexin called calmegin has been described (33), and calmegin knock-out mice are infertile (34). An entire testis-specific thioredoxin system also exists in developing spermatids, comprising Sptrx-1, Sptrx-2, and Sptrx-3 (35). The range of testis-specific redox proteins is remarkable, yet the precise function of ER proteins in the gonads is poorly understood.…”