DAX-1 and DAX-1A expression in human testicular tissues with primary spermatogenic failure.

Abstract

DAX-1 [dosage-sensitive sex reversal-adrenal hypoplasia congenital (AHC) critical region on the X chromosome gene 1; NR0B1] is an orphan nuclear receptor that acts as a transcriptional repressor in adrenal/gonadal development, steroidogenesis and probably spermatogenesis. An alternatively spliced form called DAX-1A (NR0B1A) has been described in several tissues including the testis, and in vitro studies have shown an inhibitory effect on DAX-1 transcriptional function. We aimed to study the mRNA and protein expression of DAX-1 in testicular tissues of 65 men with primary spermatogenic failure [complete Sertoli cell only syndrome (SCOS), focal SCOS, maturation arrest and mixed atrophy] compared with 33 controls with normal spermatogenesis. As a novel finding, we observed intense immunostaining, not only in the nucleus of Sertoli cells, but also in pachytene spermatocytes and round spermatids. The quantitative mRNA expression of DAX-1 and DAX-1A was similar between cases and controls and was not associated with the levels of gonadotrophins and steroids. Moreover, DAX-I transcript expression level was ∼750-fold higher than DAX-1A, and there was a strong positive correlation between them (r = 0.52; P< 0.001). We conclude that, in addition to Sertoli cells, DAX-1/DAX-1A is expressed in germ cells from spermatogonia to round spermatids. Besides, the similar mRNA expression of DAX-I and DAX-IA in testicular tissues from cases and controls does not support the involvement of DAX-1 in the etiology of primary spermatogenic failure. Finally, the low level of expression of the alternative transcriptional variant DAX-1A would not support its putative inhibitory function in vivo.

• Authors: M C Lardone, A Parada-Bustamante, M Ebensperger, R Valdevenito, E Kakarieka, D Martínez, R Pommer, A Piottante, A Castro
• Journal: Molecular human reproduction (Mol Hum Reprod) Vol. 17 Issue 12 Pg. 739-46 (Dec 2011) ISSN: 1460-2407 [Electronic] England
• PMID: 21775412 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DAX-1 Orphan Nuclear Receptor
• Gonadotropins
• NR0B1 protein, human
• Protein Isoforms
• RNA, Messenger
• Steroids

Topics

• Adult
• Alternative Splicing
• Case-Control Studies
• Chile
• DAX-1 Orphan Nuclear Receptor (genetics, metabolism)
• Gene Expression
• Gonadotropins (biosynthesis)
• Humans
• Immunohistochemistry
• Male
• Protein Isoforms (genetics, metabolism)
• RNA, Messenger (analysis)
• Real-Time Polymerase Chain Reaction
• Reproduction (genetics)
• Sertoli Cell-Only Syndrome (genetics)
• Sertoli Cells (metabolism, pathology)
• Spermatids (cytology, metabolism)
• Spermatocytes (cytology, metabolism)
• Spermatogenesis
• Spermatogonia (cytology, metabolism)
• Steroids (biosynthesis)