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

Abstract

Mammalian germ cells are endowed with a complete set of thioredoxins (Trx), a class of redox proteins located in specific structures of the spermatid and sperm tail. We report here the characterization, under normal and pathological conditions, of a novel thioredoxin with a germ line-restricted expression pattern, named spermatocyte/spermatid-specific thioredoxin-3 (SPTRX-3). The human SPTRX-3 gene maps at 9q32, only 50 kb downstream from the TRX-1 gene from which it probably originated as genomic duplication. Therefore, human SPTRX-3 protein comprises a unique thioredoxin domain displaying high homology with the ubiquitously expressed TRX-1. Among the tissues investigated, Sptrx-3 mRNA is found exclusively in the male germ cells at pachytene spermatocyte and round spermatid stages. Light and electron microscopy show SPTRX-3 protein to be predominately located in the Golgi apparatus of pachytene spermatocytes and round and elongated spermatids, with a transient localization in the developing acrosome of round spermatids. In addition, increased levels of SPTRX-3, possibly caused by overexpression, are observed in morphologically abnormal human spermatozoa from infertile men. In addition, SPTRX-3 is identified as a novel postobstruction autoantigen. In this report, we propose that SPTRX-3 can be used as a specific marker for diverse sperm and testis pathologies. SPTRX-3 is the first thioredoxin specific to the Golgi apparatus, and its function within this organelle might be related to the post-translational modification of proteins required for germ cell-specific functions, such as acrosomal biogenesis.

Cellular localization of sphingomyelin synthase 2 in the seminiferous epithelium of adult rat testes

“…For instance, the expression of a spermatocyte/spermatid-specific thioredoxin-3 was shown to be significantly reduced in aberrant spermatogenesis (Jimenez et al 2004). In addition, the inability of spermatozoa to undergo acrosome reaction is clinically known to be one of the causes of male infertility (Benoff 1997).…”

Molecular analysis of testis biopsy and semen pellet as complementary methods with histopathological analysis of testis in non-obstructive azoospermia

“…Due to its expression in spermatogonia, TSPY1 can be used as a marker for presence of spermatogonial cells. Spermatocyte/spermatidspecific thioredoxin-3 (SPTRX3) is related to thioredoxin protein family and is expressed in pachytene spermatocytes and round spermatids [13]. Spermatid-specific thioredoxin-1 (SPTRX1) is another member of thioredoxin protein family and is expressed exclusively in round and elongating spermatid [14].…”

Absolute mRNA levels and transcriptional regulation of the mouse testis-specific thioredoxins

“…Moreover, different forms of thioredoxins and thioredoxin reductases with unique properties such as organelle-or tissue-specific localization have been reported [6][7][8][9][10][11]. In this regard, male germ cells are endowed with three testis-specific thioredoxins named Sptrx-1 [12,13], Sptrx-2 [14,15] and Sptrx-3 [16], respectively, thus reflecting a key role of this family of proteins in spermatogenesis.…”

“…Sptrx-2 could be involved in the reduction of disulfide bonds within the sperm fibrous sheath components [14,15]. In contrast to Sptrx-1 and Sptrx-2, the Sptrx-3 gene codes for a unique thioredoxin domain and was originated as a genomic duplication of the Trx-1 gene [16]. Sptrx-3 is a Golgi apparatus-associated thioredoxin showing a transient association with the developing spermatid acrosome.…”

“…Sptrx-3 is a Golgi apparatus-associated thioredoxin showing a transient association with the developing spermatid acrosome. Its function might be related to the post-translational modification of proteins required for acrosomal biogenesis [16].…”