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.
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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)
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Chemical References |
- DAX-1 Orphan Nuclear Receptor
- Gonadotropins
- NR0B1 protein, human
- Protein Isoforms
- RNA, Messenger
- Steroids
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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)
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